Schisandra B inhibits proliferation, migration and invasion of bladder cancer by regulating the Wnt/β‑catenin signaling pathway

Objective:To investigate the effects of Schisandra B on proliferation,migration,invasion of bladder cancer and to further investigate its molecular mechanism.Methods:Bladder cancer cells were subjected to different concentrations of Schisandra B solution(0,20,40,80μmol/L).CCK-8 assay was used to detect the effect of schisandra B on bladder cancer cell proliferation.Transwell migration assay and wound healing assay were used to detect the effect of Schisandra B on the migration of bladder cancer cells.Transwell invasion assay was used to detect the effect of schisandra B on invasion ability of bladder cancer cells.The expression levels of intracellularβ-catenin and c-myc protein were measured by western blot.Results:Schisandra B inhibited the proliferation of T24 and UM-UC-3 cells in a concentration and time dependent manner(P<0.05).The rate of wound healing and number of migration and invasion cells decreased with the increase of Schisandra B concentration(P<0.05).The expression ofβ-catenin and c-myc decreased after treatment with Schisandra B in bladder cancer cells(P<0.05).Conclusion:Schisandra B can inhibit the proliferation,migration and invasion of human bladder cancer T24 and UM-UC-3 cells,and the main mechanism for its inhibitory effect may be related to the inactivation of the Wnt/β-catenin signaling pathway.

Mechanisms of inhibition by aspirin of endometrial carcinoma cell proliferation, migration and invasion

Objective:To investigate the effects and mechanisms of aspirin on the proliferation,migration and invasion of endometrial carcinoma HEC-1 A cell lines.Methods:HEC-1 Acells were cultured to the exponential phase and treated with different concentrations of aspirin(0.625 mmol/L,1.25 mmol/L,2.5 mmol/L,5 mmol/L and 10 mmol/L)for 24 to 120 hours.Cell proliferation was assessed by methyl thiazolyl tetrazolium(MTT)assay.The migration and invasion of HEC-1 Acells were detected by transwell assay.The protein expressions of vascular endothelial growth factor(VEGF)and ascular endothelial growth factor receptor 2(VEGFR-2)in HEC-1 Acells were determined by western blotting.Results:MTT results showed that aspirin inhibited the growth and proliferation of endometrial cancer cells in concentration and time-dependent manner.Aspirin had a significant inhibitory effect on the migration and invasion of HEC-1 Acells(P<0.05).In addition,aspirin obviously suppressed concentration-dependently the expression levels of VEGF and VEGFR-2(P<0.05).Conclusion:Aspirin could inhibit the proliferation,migration and invasion of endometrial cancer cells.The anti-tumor mechanism of aspirin might be related to the inhibition of tumor angiogenesis via blocking the VEGF/VEGFR-2 signaling pathway.

TRIP13 is identified as a prognosis biomarker for renal clear cell carcinoma and promotes renal cell carcinoma cell proliferation, migration and invasion

This work aimed to discover new therapeutic targets in renal clear cell carcinoma by bioinformatics and detect the effect of candidate gene TRIP13 in renal cell carcinoma(RCC)cell proliferation,migration,and invasion.Differentially expressed mRNAs were screened based on The Cancer Genome Atlas(TCGA)-Kidney Renal Clear Cell Carcinoma(KIRC)databases,and functional enrichments,survival analysis,receiver operating characteristic curve(ROC),and Protein–Protein Interaction(PPI)protein interaction analysis were performed by R software to screen the candidate gene TRIP13.Then,the expression of candidate gene TRIP13 in 92 pairs of cancer and adjacent normal tissues of renal clear cell carcinoma patients were detected by qRT-PCR,western blotting,and immunochemical analysis.The TRIP13 level and clinicopathological characteristics of patients with renal clear cell carcinoma were analyzed.Using 186-O and ACHN RCC cell lines with TRIP13 overexpressing or downregulating,the effect of TRIP13 on cell viability and proliferation were detected by CCK8 and EdU staining,respectively.The migration and invasion were detected by Transwell assays.A total of 19858 differentially expressed genes,5823 differentially expressed genes,3657 up-regulated genes,and 2166 down-regulated genes were identified.TRIP13 was closed associated with cell cycle regulation,and survival and prognosis of renal clear cell carcinoma were selected as a candidate gene.The mRNA and protein levels of TRIP13 in cancer tissues were higher than that in adjacent normal tissues.TRIP13 level was significantly associated with tumor size,tumor stage,Fuhrman grade,and lymph node metastasis.TRIP13 overexpression significantly increased cell viability,proliferation,migration,and invasion,while downregulating of TRIP13 had opposite effects in both 186-O and ACHN cells.Therefore,TRIP13 promotes RCC proliferation and metastasis,which should be a novel biomarker for early diagnosis,treatment,and prognosis of RCC.

KIFC3 promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells by activating EMT and β-catenin signaling

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies.A total of 45 kinesin superfamily proteins(KIFs)have been identified in humans,among which several family members have demonstrated varied functions in tumor pathobiology via different mechanisms,including regulation of cell cycle progression and metastasis.KIFC3 has microtubule motor activity and is involved in cancer cell invasion and migration,as well as survival.However,the role of KIFC3 in ESCC is still unknown.AIM To evaluate the role of KIFC3 in ESCC and the underlying mechanisms.METHODS Expression of KIFC3 was evaluated in ESCC tissues and adjacent normal esophageal tissues.The prognostic value of KIFC3 was analyzed using Kaplan-Meier Plotter.Colony formation,EdU assays,cell cycle analysis,Transwell assay,immunofluorescence,and western blotting were performed in ESCC cell lines after transfection with pLVX-Puro-KIFC3-shRNA-and pLVX-Puro-KIFC3-expressing lentiviruses.A xenograft tumor model in nude mice was used to evaluate the role of KIFC3 in tumorigenesis.Inhibitor ofβ-catenin,XAV-939,was used to clarify the mechanism of KIFC3 in ESCC.To analyze the differences between groups,t test and nonparametric tests were used.P<0.05 was considered statistically significant.RESULTS Immunohistochemical staining indicated that KIFC3 was upregulated in ESCC tissues compared with adjacent normal tissues.Kaplan-Meier Plotter revealed that overexpressed KIFC3 was associated with poor prognosis in ESCC patients.Colony formation and EdU assay showed that KIFC3 overexpression promoted cell proliferation,while KIFC3 knockdown inhibited cell proliferation in ESCC cell lines.In addition,cell cycle analysis showed that KIFC3 overexpression promoted cell cycle progression.KIFC3 knockdown suppressed ESCC tumorigenesis in vivo.Transwell assay and western blotting revealed that KIFC3 overexpression promoted cell migration and invasion,as well as epithelial-mesenchymal transition(EMT),while KIFC3 knockdown showed the opposite results.Mechanistically,KIFC3 overexpression promoted β-catenin signaling in KYSE450 cells;however,the role of KIFC3 was abolished by XAV-939,the inhibitor of β-catenin signaling.CONCLUSION KIFC3 was overexpressed in ESCC and was associated with poor prognosis.Furthermore,KIFC3 promoted proliferation,migration and invasion of ESCC via β-catenin signaling and EMT.

Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway

Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.

IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells

Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.

Effect of Cx32 over‑expression on cell proliferation, migration, and invasion of hepatocellular carcinoma cell line Huh7 and its mechanism

Objective: To explore the effect of connexin 32 (Cx32) on the cell proliferation, migration, invasion of human hepatocellular carcinoma (HCC) cell line Huh7 and its mechanism. Methods: Firstly, bioinformatics techniques were used to analyze the difference in expression of Cx32 between HCC tissues and normal liver tissues, and the relationship between Cx32 expression and important clinicopathological features of HCC was also explored. Subsequently, Cx32 expression in HCC cell lines and normal hepatic epithelial cell line was detected in vitro. Huh7 cell line with stable over⁃expression of Cx32 was further established, and the change in cell proliferation ability was measured by MTT assay, changes in migration and invasion capacities were detected by wound⁃healing assay and transwell assay, on this cell line. Finally, western blot and immunofluorescence (IF) were used to investigate the alterations of expression of epithelial⁃mesenchymal transition (EMT) markers. Results: Bioinformatics analyses showed that Cx32 mRNA and protein expression levels in HCC tissues were lower than those in normal liver tissues, and the mRNA expression level of Cx32 was negatively correlated with T stage, histological grade and clinical stage of HCC patients (all P<0.05). Results of in vitro experiments revealed Cx32 protein expression in different HCC cell lines was down⁃regulated compared to that in normal hepatic epithelial cell line LO2. Cx32 stably over⁃expressed (Cx32 OE) Huh7 cell line was successfully constructed by lentivirus infection and showed high expression of Cx32 protein in the cell line. Compared to the control group and (or) the negative control (NC) group, the Cx32 OE group exhibited decreased OD490 value, wound healing rate and invasive cell number (all P<0.05). Furthermore, an increase in the expression of epithelial marker E⁃cadherin, and a decrease in the expression of mesenchymal markers Snail and Vimentin, were observed in Cx32⁃OE Huh7 cell line. Conclusion: Cx32 is low expressed in HCC tissues and cells, while the proliferation, migration and invasion ability of Huh7 cells can be inhibited by over⁃expression of Cx32, of which the underlying mechanism may be related to the inhibition of EMT process.

Effect of Interferon Regulatory Factor 1 on Proliferation,Invasion and Migration of Tongue Squamous Carcinoma Cells and Its Mechanism

[Objectives]This study was conducted to investigate the effect of interferon regulatory factor on the invasion and migration of tongue squamous carcinoma cells. [Methods]The expression level of IRF1 in tongue squamous carcinoma tissues was detected by real-time quantitative PCR and immunohistochemistry. Plasmids for overexpression and knockdown of IRF1 were constructed. The effects of overexpression and knockdown of IRF1 on the proliferation, invasion and migration of Tca8113 cells were examined in Tca8113 cells. [Results] IRF1 expression was abnormally reduced in tongue squamous carcinoma tissues, and both real-time quantitative PCR and immunohistochemistry showed significantly lower expression than that of paraneoplastic controls. The overexpression and knockdown plasmids of IRF1 were successfully constructed. Growth curve assays showed that overexpression of IRF1 inhibited the proliferation of Tca8113 cells, while knockdown of IRF1 promoted the proliferation of Tca8113 cells. Scratch assay showed that overexpression of IRF1 inhibited the migration of Tca8113 cells, while knockdown of IRF1 promoted the migration of Tca8113 cells. Transwell assay showed that overexpression of IRF1 inhibited the invasion of Tca8113 cells, while knockdown of IRF1 promoted the invasion of Tca8113 cells. [Conclusions] In the development of tongue squamous carcinoma, IRF1 functions as an anti-oncogene, and the expression level of IRF1 was reduced in tongue squamous carcinoma tissues.

TATA-box-binding protein-associated factor 15 is a novel biomarker that promotes cell proliferation and migration in gastrointestinal stromal tumor

BACKGROUND Gastrointestinal stromal tumor(GIST)is a common neoplasm with high rates of recurrence and metastasis,and its therapeutic efficacy is still not ideal.There is an unmet need to find new molecular therapeutic targets for GIST.TATA-boxbinding protein-associated factor 15(TAF15)contributes to the progress of various tumors,while the role and molecular mechanism of TAF15 in GIST progression are still unknown.AIM To explore new molecular therapeutic targets for GIST and understand the biological role and underlying mechanisms of TAF15 in GIST progression.METHODS Proteomic analysis was performed to explore the differentially expressed proteins in GIST.Western blotting and immunohistochemical analysis were used to verify the expression level of TAF15 in GIST tissues and cell lines.Cell counting kit-8,colony formation,wound-healing and transwell assay were executed to detect the ability of TAF15 on cell proliferation,migration and invasion.A xenograft mouse model was applied to explore the role of TAF15 in the progression of GIST.Western blotting was used to detect the phosphorylation level and total level of RAF1,MEK and ERK1/2.RESULTS A total of 1669 proteins were identified as differentially expressed proteins with 762 upregulated and 907 downregulated in GIST.TAF15 was selected for the further study because of its important role in cell proliferation and migration.TAF15 was significantly over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with larger tumor size and higher risk stage of GIST.TAF15 knockdown significantly inhibited the cell proliferation and migration of GIST in vitro and suppressed tumor growth in vivo.Moreover,the inhibition of TAF15 expression significantly decreased the phosphorylation level of RAF1,MEK and ERK1/2 in GIST cells and xenograft tissues,while the total RAF1,MEK and ERK1/2 had no significant change.CONCLUSION TAF15 is over expressed in GIST tissues and cell lines.Overexpression of TAF15 was associated with a poor prognosis of GIST patients.TAF15 promotes cell proliferation and migration in GIST via the activation of the RAF1/MEK/ERK signaling pathway.Thus,TAF15 is expected to be a novel latent molecular biomarker or therapeutic target of GIST.

Eriocitrin inhibits proliferation and migration of lung adenocarcinoma cells by regulating epithelial mesenchymal transition

Objective:To investigate the effects of Eriocitrin on the proliferation and migration of Lung adenocarcinoma(LUAD)cells A549 and H1299,and the mechanism of Epithelial-Mesenchymal Transition(EMT).Methods:The effects of different Eriocitrin on the proliferation of LUAD cells A549 and H1299 were examined by CCK8 method.EMT-associated epithelial calmodulin(E-cadherin and N-cadherin),vimentin,ferroptosis-associated protein SLC7A11,GPX4,FTH were detected by Western Blot and expression of mRNA of EMT marker molecules E-cadherin,N-cadherin,Snail were detected by qRT-PCR.Effects of saccharomyces cerevisiae suberin on ferroptosis in LUAD cells as observed by lipid reactive oxygen species(ROS)assay.Results:Eriocitrin could significantly inhibit the proliferative behavior of LUAD cells A549 and H1299 and showed a certain dose-and time-dependence.Compared with the control group,different concentrations of Eriocitrin could significantly reduce the scratch healing rate after 24 and 48 h of action,and the difference was statistically significant(P<0.01).The expression of ROS is increased,EMT-related protein E-cadherin was increased in LUAD cells A549 and H1299 compared with the control group after the intervention with Eriocitrin.N-cadherin and Vimentin expression was decreased.E-cadherin mRNA expression was increased,and N-cadherin,Snail mRNA expression was decreased,expression of ferroptosis-associated protein SLC7A11,GPX4,FTH was decreased,the difference was statistically significant(P<0.05).Conclusion:Eriocitrin may inhibit the proliferation and migration of LUAD cells by regulating the EMT pathway and has potential application in LUAD prevention and adjuvant chemotherapy.

Study on the mechanism of tRNA-ValAAC-5 in promoting the proliferation and migration of hepatocellular carcinoma cells

Objective:To demonstrate the role and mechanism of tRNA-ValAAC-5 expression in hepatocellular carcinoma(HCC)cells.Methods:The expression levels of tRNA-ValAAC-5 in HCC(Hep3B,HuH7,SNU398,Hep3G2)and human hepatocellular carcinoma(THLE2,THLE3)were detected by real-time PCR.HEP3B and Hep3G2 cells were respectively transfected with tRNA-ValAAC-5-inhibitor and tRNA-ValAAC-5-NC as the inhibitor group and the NC group.Then the ability of cell proliferation was detected by CCK-8 assay and the ability of invasion and metastasis was detected by Transwell assay.The protein expression levels of p21,Matrix metalloproteinase 2(MMP2)and Matrix metalloproteinase 9(MMP9)were determined by Western blot.Results:The relative expression of tRNA-ValAAC-5 in Hep3B,HuH7,SNU398 and Hep3G2 cells were significantly higher than THLE2 and THLE3 cells,the differences were statistically significant(P<0.05).After tRNA-ValAAC-5-inhibitor transfection,the expression of tRNA-ValAAC-5 in Hep3B and Hep3G2 cells were reduced than tRNA-ValAAC-NC group.Both of the differences were statistically significant(t=36.52,27.45,P<0.001),which indicated the transfection was successful.The proliferative ability of Hep3B and Hep3G2 cells transfected with tRNA-ValAAC-5-inhibitor after 24,48,72,96 h were inhibited effectively compared with tRNA-ValAAC-5-NC group.All of the differences were statistically significant in Hep3B(t=5.25,8.23,7.33,14.16,P<0.001)and Hep3G2(t=4.25,5.11,9.39,7.59,P<0.001)cells.The number of invasion and metastasis of Hep3B and Hep3G2 cells were reduced in tRNA-ValAAC-5-inhibitor group compared with tRNA-ValAAC-5-NC group,there was significant difference(t=14.01,21.85,P<0.001).The protein expression levels of P21 were lower,MMP2 and MMP9 were higher in tRNA-ValAAC-5-inhibitor group compared with tRNA-ValAAC-5-NC group,the differences were statistically significant in Hep3B(t=8.96,12.80,4.652,P<0.001)cells and Hep3G2(t=15.17,22.36,12.61,P<0.001)cells.Conclusion:tRNA-ValAAC-5 can effectively promote the proliferation,invasion and metastasis of HCC,and its possible mechanism is related to regulating the expression of p21,MMP2 and MMP9.

m^(6)A modification promotes the proliferation and migration of cervical cancer and regulates the expression of PD-L1

Objective:To explore the effects of N6-methyladenine(m^(6)A)modification-related genes,methyltransferase 14(METTL14),and YTH domain family protein 1(YTHDF1),on the proliferation,migration and apoptosis capabilities of cervical cancer cells and investigate their correlation with programmed cell death-ligand 1(PD-L1)expression.Methods:The expression levels of METTL14,YTHDF1 and PD-L1 in cervical cancer tissues and normal cervical tissues were analyzed using immunohistochemistry.Small interfering RNA(siRNA)was used to knock down the expression of METTL14 and YTHDF1 genes in cervical cancer cells,and the knockdown efficiency was validated by real-time fluorescent quantitative PCR(qPCR).After knockdown of METTL14 and YTHDF1,cell proliferation was assessed by CCK-8 assay,cell migration was examined by Transwell assay,cell apoptosis was detected by flow cytometry,and PD-L1 mRNA and protein expression were evaluated using qPCR and Western blotting,respectively.Results:Immunohistochemistry results demonstrated high expression of METTL14,YTHDF1,and PD-L1 in cervical cancer tissues.Knockdown of METTL14 and YTHDF1 significantly inhibited the proliferation and migration capabilities of cervical cancer cells,increased apoptosis,and downregulated PD-L1 mRNA and protein expression levels.Conclusion:m^(6)A methylation modification can affect the proliferation,migration and apoptosis of cervical cancer cells by regulating the expression of PD-L1 in cervical cancer cells.

Effects of JAG-1 on the Proliferation and Migration of Gastric Adenocarcinoma Cells after TRAIP Knockout

[Objectives]To study the effects of JAG-1 on silencing TRAIP(tumor necrosis factor receptor associated factor interaction protein)after regulating Notch signaling pathway on the proliferation and migration of gastric adenocarcinoma cells.[Methods]Gastric adenocarcinoma cells were categorized into si-NC+DMSO(control+DMSO),si-TRAIP#1+DMSO(transfected with TRAIP+DMSO),si-NC+JAG-1(control+JAG-1),and si-TRAIP#1+JAG-1(transfected with TRAIP+JAG-1),and the proliferation of the cells was detected by CCK-8 assay and plate colony formation assay.Transwell assay was used to detect cell migration,and Western blot was adopted to detect the expression of proliferation-associated protein CyclinD1,migration-associated protein MMP2,and key proteins of Notch signaling pathway Notch1,Hes1 and Jagged1.[Results]Compared with siTRAIP#1+DMSO,the gastric adenocarcinoma cells in si-TRAIP#1+JAG-1 group showed increased proliferation and migration(P<0.05),and there was a significant increase in the expression of CyclinD1,MMP2,Notch1,Hes1,and Jagged1(P<0.05).[Conclusions]After TRAIP knockdown,JAG-1 increased not only the proliferation and migration ability of gastric adenocarcinoma cells,but also the expression of key proteins of Notch signaling pathway Notch1,Hes1,and Jagged1.

Ezrin Promotes the Proliferation, Migration, and Invasion of Ovarian Cancer Cells

Objective The underlying mechanism of Ezrin in ovarian cancer(OVCA) is far from being understood.Therefore, this study aimed to assess the role of Ezrin in OVCA cells(SKOV3 and Ca OV3) and investigate the associated molecular mechanisms.Methods We performed Western blotting, reverse transcription-quantitative polymerase chain reaction, MTT, cell colony, cell wound healing, transwell migration and invasion, Rho A and Rac active pull down assays, and confocal immunofluorescence experiments to evaluate the functions and molecular mechanisms of Ezrin overexpression or knockdown in the proliferation and metastasis of OVCA cells.Results The ectopic expression of Ezrin significantly increased cell proliferation, invasiveness, and epithelial–mesenchymal transition(EMT) in OVCA cells. By contrast, the knockdown of endogenous Ezrin prevented OVCA cell proliferation, invasiveness, and EMT. Lastly, we observed that Ezrin can positively regulate the active forms of Rho A rather than Rac-1 in OVCA cells, thereby promoting robust stress fiber formation.Conclusion Our results indicated that Ezrin regulates OVCA cell proliferation and invasiveness by modulating EMT and induces actin stress fiber formation by regulating Rho-GTPase activity, which provides novel insights into the treatment of the OVCA.

Effects of polydatin on the proliferation,migration,and invasion of ovarian cancer

To investigate the effects of polydatin on the proliferation,migration,and invasion of ovarian cancer,the change of proliferative ability,migration ability,and invasive ability of human ovarian cancer cell OVCAR-3,A2780,and HO-8910 was detected by using polydatin and up-regulating PI3K.The anticancer activity and mechanism of polydatin in ovarian cancer were analyzed.Polydatin could effectively inhibit the proliferation,migration,and invasion of OVCAR-3,A2780,and HO-8910,and inhibit the expression of PI3K protein.After the expression level of PI3K protein was up-regulated,the inhibitory effect of polydatin on the proliferative ability,migration ability,and invasive ability of OVCAR-3,A2780,and HO-8910 significantly decreased,suggesting that PI3K was the target of polydatin.Therefore,we concluded that polydatin could inhibit the proliferation,migration,and invasion of ovarian cancer cells by inhibiting the expression of PI3K protein,which provides an experimental basis for polydatin in the treatment of ovarian cancer.

Effects and Mechanism of Oxymatrine on Proliferation,Invasion and Migration of Hepatocellular Carcinoma Cells

[Objectives] To observe the effects of oxymatrine on the proliferation,invasion and migration of hepatocellular carcinoma cells,and to explore its possible molecular mechanism.[Methods]The hepatocellular carcinoma cell line Hep G2 was randomly divided into the negative control group and the low,medium and high concentration groups of oxymatrine.The negative control group was added to the cell culture medium,and the low,medium and high concentration groups of oxymatrine were added to the oxymatrine and cell culture medium with the final concentration of 1.0,2.0 and 4.0 mg/m L.The proliferation of each group was measured by MTT assay,and the inhibition rate of cell proliferation was calculated.The invasion and migration ability of each group was determined using Transwell chamber assay.The expression of E-cadherin and CD44 mRNA in each group was detected using Real-time PCR,while the expression of E-cadherin and CD44 protein was detected using Western blotting method.[Results] The inhibition rate of cell proliferation in the high concentration group of oxymatrine was higher than that in the medium and low concentration groups,and the inhibition rate of cell proliferation of medium concentration group was higher than that in the low concentration group.In the cell invasion and cell migration experiments,the number of transmembrane cells of low,medium and high concentration groups of oxymatrine was less than that in the negative control group(P < 0.05),the number of transmembrane cells of high concentration groups of oxymatrine was less than that in medium and low concentration groups,and the number of transmembrane cells of medium concentration group was less than in that of the low concentration group(P < 0.05).Compared with the negative control group,the expression of E-cadherin mRNA and protein increased in the low,medium and high concentration groups of oxymatrine,while the expression of CD44 mRNA and protein decreased(P < 0.05).[Conclusions] Oxymatrine has the effect of inhibiting the proliferation,invasion and migration of hepatocellular carcinoma cell line Hep G2 in vitro.The higher the concentration,the more significant the effect will be.The mechanism is possibly connected with the up-regulation of E-cadherin expression and down-regulation of CD44 expression.

Mechanism of SCD1 in promoting proliferation,migration and invasion of human papillary thyroid cancer cells

Objective:To investigate the effects of SCD1 on the proliferation,migration and invasion of human papillary thyroid cancer cell line TPC1.Methods:The expression of SCD1 in human thyroid follicular epithelial normal cells Nthy-ori 3-1 and thyroid papillary carcer cell lines TPC1,BCPAP and K1 was detected by Western blot.The negative control and SCD1 siRNA were transfected respectively into human thyroid papillary carcer cell line TPC1,then the expressions of SCD1 mRNA and protein in each group were tested by real-time fluorescence quantitative PCR(qRT-PCR)and Western blot.The effects of interfering SCD1 on the proliferation,migration and invasion of TPC1 cells were detected by CCK-8 method and Transwell chamber assay respectively.Meanwhile,the expression levels of epithelial-mesenchymal transition(EMT)related proteins(N-cadherin,Snail,vimentin and E-cadherin)were detected by qRT-PCR and Western blot.Results:The expression level of SCD1 in TPC1 was significantly higher than that in Nthy-ori 3-1,BCPAP and K1(P<0.05).Compared with the blank control group(Control)and the control interference group(si-NC),the expression of SCD1 mRNA and protein in the interference SCD1 group(si-SCD1)was significantly decreased(P<0.05).The proliferation,migration and invasion of TPC1 cells were significantly inhibited after interfering with SCD1(P<0.05).It was also found that interfering SCD1 could increase the expression of E-cadherin protein while the expression of vimentin,Snail and N-cadherin protein were inhibited significantly(P<0.05).Conclusion:Interfering SCD1 was able to inhibit the proliferation,migration and invasion of thyroid papillary cancer cell TPC1 with the potential mechanism by inhibition of the EMT procedure.

How is the AKT/mTOR pathway involved in cell migration and invasion?

As a pathway that plays a role in nutrient absorption,anabolic response,cell growth and survival,the important role of AKT/mTOR in tumorigenesis has also come to light.For cancer patients,most deaths are caused by the growth of metastatic tumors outside the primary focus.Therefore,migration and invasion in the late stage of tumor progression are the main unresolved issues in the study of tumor pathogenesis,and AKT/mTOR has been found to participate in the migration and invasion of cancer cells,which means that the study of this pathway may contribute to a solution for the problem.Because of its extensive and complex functions in the organism,this pathway can be regulated by a variety of different signals in the body,and then realize its function through different downstream signal molecules.This article reviews the proteins that can indirectly affect this pathway by regulating the common upstream signaling molecules of this pathway,and the proteins that can directly affect the level of phosphorylation of AKT/mTOR in cancer cells.We also review the proteins that can co-regulate this pathway and its downstream pathways.Through this study,we hope to gain a deeper understanding of the regulatory mechanism of the AKT/mTOR pathway in cancer cells,in hopes of finding effective and harmless cancer treatment targets in the future.

High Expression of CDCA7 Promotes Cell Proliferation, Migration, Invasion and Apoptosis in Non-Small-Cell Lung Cancer

Objective Increased expression of CDCA7 is associated with a poorer prognosis in patients with non-small-cell lung cancer(NSCLC).This study was performed to investigate the effects of down-regulating cell division cycle-associated 7(CDCA7)gene expression on the proliferation,migration,invasion,cell cycle and apoptosis of human NSCLC cell lines.Methods Cultured A549 and NCI-H292 cells were transfected with si NC(control group)or si CDCA7(experimental group).Cell activity was detected using the CCK-8 and a Real Time Cell Analyzer(RTCA).Cell migration and invasion were also measured by RTCA.In addition,flow cytometry was used to assess the cell cycle progression and apoptosis in the cells,and Western blotting was used to detect the expression level of proteins in key signaling pathways.Results Compared with the cells transfected with si NC,the cell proliferation was significantly reduced(P<0.05),the migration and invasion were decreased,and the cell cycle was blocked in the G0/G1 phase(P<0.05)in the cells transfected with si CDCA7.The number of cells undergoing apoptosis was also increased(P<0.05).Western blotting revealed that P-ERK,Cyclin-D1,Vimentin and Bcl-2 were all downregulated.However,the expression of E-cadherin was not affected by the down-regulation of CDCA7,suggesting that it is upstream of this gene.Conclusion Silencing the CDCA7 gene inhibited the proliferation,migration and invasion of A549 and NCI-H292 cells,hindered the cell cycle transition to the S phase,and promoted cell apoptosis.These findings indicate that CDCA7 may represent a new therapeutic target for NSCLC.