Objective： The mechanisms by which lipopolysaccharide （LPS） pretreatment induces cardioprotection following ischaemia/reperfusion （I/R） have not been fully elucidated. We hypothesized that activation of phosphoin...Objective： The mechanisms by which lipopolysaccharide （LPS） pretreatment induces cardioprotection following ischaemia/reperfusion （I/R） have not been fully elucidated. We hypothesized that activation of phosphoinositide 3-kinase （PI3K）/Akt and high mobility group box 1 （HMGBxl） signaling plays an important role in LPS-induced cardioprotection. Methods： In in vivo experiments, age- and weight- matched male C57BL/10Sc wild type mice were pretreated with LPS before ligation of the left anterior descending coronary followed by reperfusion. Infarction size was examined by triphenyltetrazolium chloride （TTC） staining. Akt, phospho-Akt, and HMGBxl were assessed by immunoblotting with appropriate primary antibodies. In situ cardiac myocyte apop- tosis was examined by the TdT-mediated dUTP nick-end labeling （TUNEL） assay. In an in vitro study, rat cardiac myoblasts （H9c2） were subdivided into two groups, and only one was pretreated with LPS. After pretreatment, the cells were transferred into a hypoxic chamber under 0.5% 02. Levels of HMGBxl were assessed by immunoblot. Results： In the in vivo experiment, pretreatment with LPS reduced the at risk infarct size by 70.6% and the left ventricle infarct size by 64.93% respectively. Pretreatment with LPS also reduced cardiac myocytes apoptosis by 39.1% after ischemia and reperfusion. The mechanisms of LPS induced cardioprotection involved increasing PI3K/Akt activity and decreasing expression of HMGBxl. In the in vitro study, pretreatment with LPS reduced the level of HMGBxl in H9c2 cell cytoplasm following hypoxia. Conclusion： The results suggest that the cardioprotection following I/R induced by LPS pretreatment involves PI3K/Akt and HMGBxl pathways.展开更多
BACKGROUND Mounting studies have highlighted the pivotal influence of anti-silencing function 1B(ASF1B)on the malignancy of cancers.AIM To explore the influence and mechanism of ASF1B in colorectal cancer(CRC).METHODS...BACKGROUND Mounting studies have highlighted the pivotal influence of anti-silencing function 1B(ASF1B)on the malignancy of cancers.AIM To explore the influence and mechanism of ASF1B in colorectal cancer(CRC).METHODS Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expression of ASF1B.Immunohistochemical staining was performed to detect protein expression of ASF1B and Ki67 in tumor tissues.Western blot analysis was used to determine levels of ASF1B and proliferation/epithelial mesenchymal transition(EMT)/stemness-related proteins.In addition,the proliferation of CRC cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2’-Deoxyuridine assays.The migration and invasion of CRC cells were evaluated using transwell assays.Stemness of CRC cells was tested using the sphere formation assay.To construct a xenograft tumor model,HCT116 cells were introduced into mouse flanks via subcutaneous injection.RESULTS ASF1B expression was markedly increased in CRC tissues and cells,and it was inversely correlated with overall survival of CRC patients and was positively associated with the tumor node metastasis(TNM)stage of CRC patients.Silencing of ASF1B suppressed proliferation,migration,invasion,stemness and EMT of CRC cells as well as tumorigenesis of xenograft mice.Furthermore,protein levels of Pphosphatidylinositol 3-kinase(p-PI3K)and p-AKT were decreased after silencing of ASF1B in CRC cells.The inhibitory effects of ASF1B knockdown on cell proliferation,stemness and EMT were partly abolished by PI3K activator in CRC cells.CONCLUSION Silencing of ASF1B inactivated the PI3K/AKT pathway to suppress CRC malignancy in vitro.展开更多
AIM: To investigate the role of phosphatidylinositol 3-kinase (PI 3-K)/Akt signaling pathway in the balance of HSC activation and apoptosis in rat hepatic stellate cells (HSC). METHODS: An activated HSC cell line was ...AIM: To investigate the role of phosphatidylinositol 3-kinase (PI 3-K)/Akt signaling pathway in the balance of HSC activation and apoptosis in rat hepatic stellate cells (HSC). METHODS: An activated HSC cell line was used in this study. LY 294002, the PI 3-K/Akt signal pathway block-er was used to investigate the molecular events on apoptosis in HSC and to interpret the role of this path-way in HSC apoptosis. Immunocytochemistry, Western blot and reverse transcription polymerase chain reac-tion (RT-PCR) analysis were applied to detect the ex-pression of PI 3-K, and simultaneously phosphorylated-Akt (p-Akt) and total-Akt were determined by Western blot. The HSC apoptosis was examined by annexin-V/ propidium iodide double-labelled flow cytometry and transmission electron microscopy. RESULTS: The apoptosis rates in LY 294002 (30.82% ± 2.90%) and LY 294002 + PDGF-BB (28.16% ± 2.58%) groups were signif icantly increased compared with those of control (9.02% ± 1.81%) and PDGF-BB (4.35% ± 1.18%). PDGF-BB augmented PI 3-K and p-Akt expres-sion. LY 294002 signif icantly reduced the contents of PI 3-K and p-Akt. mRNA transcription evaluated by RT-PCR showed similar tendencies as protein expression. CONCLUSION: Inhibition of PI 3-K/Akt signaling path-way induces apoptosis in HSC.展开更多
Objective To evaluate the effect of diisononyl phthalate（DINP） exposure during gestation and lactation on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. Methods Fem...Objective To evaluate the effect of diisononyl phthalate（DINP） exposure during gestation and lactation on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. Methods Female Wistar rats were treated with DINP at different dosages（0, 5, 50, and 500 mg/kg of body weight per day）. The pups were sensitized and challenged by ovalbumin（OVA）. The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin（HE） staining; and the relative cytokines in phosphoinositide 3-kinase（PI3K）/Akt pathway were measured by enzyme-linked immunosorbent assay（ELISA） and western blot analysis. Results There was no significant difference in DINP＇s effect on airway hyperresponsiveness（AHR） between male pups and female pups. In the 50 mg/（kg·d） DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance（RI） compared with those from controls（P〈0.05）. Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/（kg·d） DINP-treated group. However, in the 5 and 500 mg/（kg·d） DINP-treated pups, no significant effects were observed. Conclusion There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.展开更多
Objective: This study was designed to explore whether inhibition of the extracellular-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways can inhibit the growth of xenografts of endometr...Objective: This study was designed to explore whether inhibition of the extracellular-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways can inhibit the growth of xenografts of endometrial cancer cell lines with different estrogen receptors (ER) profiles in vivo and to provide preliminary laboratory basis for the probability of endometrial adenocarcinoma treatment with blockage of the two pathways, especially to endometrial cancer with low ER status. Methods: Human endometrial cancer Ishikawa bearing ER and HEC-1Awith low ER status cells were subcutaneously injected into BALB/c nude mice to establish endometrial cancer xenograft tumor models. The effects of PI3K/Akt inhibitor LY294002, MAPK/ERK1/2 inhibitor PD-98059 and their combinations on the growth of the xenograft tumors and apoptotic state of Ishikawa and HEC-1Acells were tested in vivo using the inhibitory rate, the terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, H/E-stain. Western blot analysis was used to detect the alterations of activated ERK (P-ERK) and AKT (P-AKT) during this process. Results: LY294002, a PI3K/Akt pathway inhibitor, induced significant suppression in the growth of both Ishikawa and HEC-1Acell xenograft tumors, concomitant with increased apoptosis in xenografts as evidenced by TUNEL. A similar effect was also observed when the MAPK/ERK1/2 signaling pathway was inhibited by PD98059. Concurrent inhibition of the PI3K/Akt and MAPK/ERK1/2 pathways showed enhanced anti-tumor effects in vivo as indicated by increased apoptosis. At the same time, the levels of P-ERK and P-AKT in both xenograft tumors decreased, and their levels in combination group was the lowest. Conclusions: PD98059, LY294002 and their combinations showed remarkable inhibitory effects on xenograft tumors of endometrial carcinoma cell lines with different expression status of ER in vivo through blockage of PI3K/Akt and MAPK/ERK1/2 signaling pathways. This suggests that targeting these pathways may be an effective therapeutic strategy against endometrial carcinomas, especially for ER-negative cancers which show poor response to endocrinal therapy.展开更多
In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisi...In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.展开更多
BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPI...BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPINH1 in colorectal cancer(CRC)remain largely elusive.AIM To investigate the effects of SERPINH1 on CRC cells and its specific mechanism.METHODS Quantitative real-time polymerase chain reaction,western blotting analysis,The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues.A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC.RESULTS SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues,manifested at both mRNA and protein tiers.Elevated SERPINH1 levels correlated closely with advanced T stage,lymph node involvement,and distant metastasis,exhibiting a significant association with poorer overall survival among CRC patients.Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation,invasion,and migration in vitro,while conversely,SERPINH1 knockdown elicited the opposite effects.Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation.Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation,thereby facilitating CRC cell invasion and migration.CONCLUSION These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC,potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.展开更多
文摘Objective： The mechanisms by which lipopolysaccharide （LPS） pretreatment induces cardioprotection following ischaemia/reperfusion （I/R） have not been fully elucidated. We hypothesized that activation of phosphoinositide 3-kinase （PI3K）/Akt and high mobility group box 1 （HMGBxl） signaling plays an important role in LPS-induced cardioprotection. Methods： In in vivo experiments, age- and weight- matched male C57BL/10Sc wild type mice were pretreated with LPS before ligation of the left anterior descending coronary followed by reperfusion. Infarction size was examined by triphenyltetrazolium chloride （TTC） staining. Akt, phospho-Akt, and HMGBxl were assessed by immunoblotting with appropriate primary antibodies. In situ cardiac myocyte apop- tosis was examined by the TdT-mediated dUTP nick-end labeling （TUNEL） assay. In an in vitro study, rat cardiac myoblasts （H9c2） were subdivided into two groups, and only one was pretreated with LPS. After pretreatment, the cells were transferred into a hypoxic chamber under 0.5% 02. Levels of HMGBxl were assessed by immunoblot. Results： In the in vivo experiment, pretreatment with LPS reduced the at risk infarct size by 70.6% and the left ventricle infarct size by 64.93% respectively. Pretreatment with LPS also reduced cardiac myocytes apoptosis by 39.1% after ischemia and reperfusion. The mechanisms of LPS induced cardioprotection involved increasing PI3K/Akt activity and decreasing expression of HMGBxl. In the in vitro study, pretreatment with LPS reduced the level of HMGBxl in H9c2 cell cytoplasm following hypoxia. Conclusion： The results suggest that the cardioprotection following I/R induced by LPS pretreatment involves PI3K/Akt and HMGBxl pathways.
基金Huzhou Science and Technology Bureau Foundation,No.2018GY09.
文摘BACKGROUND Mounting studies have highlighted the pivotal influence of anti-silencing function 1B(ASF1B)on the malignancy of cancers.AIM To explore the influence and mechanism of ASF1B in colorectal cancer(CRC).METHODS Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expression of ASF1B.Immunohistochemical staining was performed to detect protein expression of ASF1B and Ki67 in tumor tissues.Western blot analysis was used to determine levels of ASF1B and proliferation/epithelial mesenchymal transition(EMT)/stemness-related proteins.In addition,the proliferation of CRC cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2’-Deoxyuridine assays.The migration and invasion of CRC cells were evaluated using transwell assays.Stemness of CRC cells was tested using the sphere formation assay.To construct a xenograft tumor model,HCT116 cells were introduced into mouse flanks via subcutaneous injection.RESULTS ASF1B expression was markedly increased in CRC tissues and cells,and it was inversely correlated with overall survival of CRC patients and was positively associated with the tumor node metastasis(TNM)stage of CRC patients.Silencing of ASF1B suppressed proliferation,migration,invasion,stemness and EMT of CRC cells as well as tumorigenesis of xenograft mice.Furthermore,protein levels of Pphosphatidylinositol 3-kinase(p-PI3K)and p-AKT were decreased after silencing of ASF1B in CRC cells.The inhibitory effects of ASF1B knockdown on cell proliferation,stemness and EMT were partly abolished by PI3K activator in CRC cells.CONCLUSION Silencing of ASF1B inactivated the PI3K/AKT pathway to suppress CRC malignancy in vitro.
基金The Natural Science Foundation of Hebei Province, China, No.C2007000843
文摘AIM: To investigate the role of phosphatidylinositol 3-kinase (PI 3-K)/Akt signaling pathway in the balance of HSC activation and apoptosis in rat hepatic stellate cells (HSC). METHODS: An activated HSC cell line was used in this study. LY 294002, the PI 3-K/Akt signal pathway block-er was used to investigate the molecular events on apoptosis in HSC and to interpret the role of this path-way in HSC apoptosis. Immunocytochemistry, Western blot and reverse transcription polymerase chain reac-tion (RT-PCR) analysis were applied to detect the ex-pression of PI 3-K, and simultaneously phosphorylated-Akt (p-Akt) and total-Akt were determined by Western blot. The HSC apoptosis was examined by annexin-V/ propidium iodide double-labelled flow cytometry and transmission electron microscopy. RESULTS: The apoptosis rates in LY 294002 (30.82% ± 2.90%) and LY 294002 + PDGF-BB (28.16% ± 2.58%) groups were signif icantly increased compared with those of control (9.02% ± 1.81%) and PDGF-BB (4.35% ± 1.18%). PDGF-BB augmented PI 3-K and p-Akt expres-sion. LY 294002 signif icantly reduced the contents of PI 3-K and p-Akt. mRNA transcription evaluated by RT-PCR showed similar tendencies as protein expression. CONCLUSION: Inhibition of PI 3-K/Akt signaling path-way induces apoptosis in HSC.
基金financially supported by the Natural Science Foundation of China(Grant Number:81072263)Shanghai Natural Science Foundation(Grant Number:10ZR1402000)
文摘Objective To evaluate the effect of diisononyl phthalate（DINP） exposure during gestation and lactation on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. Methods Female Wistar rats were treated with DINP at different dosages（0, 5, 50, and 500 mg/kg of body weight per day）. The pups were sensitized and challenged by ovalbumin（OVA）. The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin（HE） staining; and the relative cytokines in phosphoinositide 3-kinase（PI3K）/Akt pathway were measured by enzyme-linked immunosorbent assay（ELISA） and western blot analysis. Results There was no significant difference in DINP＇s effect on airway hyperresponsiveness（AHR） between male pups and female pups. In the 50 mg/（kg·d） DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance（RI） compared with those from controls（P〈0.05）. Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/（kg·d） DINP-treated group. However, in the 5 and 500 mg/（kg·d） DINP-treated pups, no significant effects were observed. Conclusion There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.
文摘Objective: This study was designed to explore whether inhibition of the extracellular-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways can inhibit the growth of xenografts of endometrial cancer cell lines with different estrogen receptors (ER) profiles in vivo and to provide preliminary laboratory basis for the probability of endometrial adenocarcinoma treatment with blockage of the two pathways, especially to endometrial cancer with low ER status. Methods: Human endometrial cancer Ishikawa bearing ER and HEC-1Awith low ER status cells were subcutaneously injected into BALB/c nude mice to establish endometrial cancer xenograft tumor models. The effects of PI3K/Akt inhibitor LY294002, MAPK/ERK1/2 inhibitor PD-98059 and their combinations on the growth of the xenograft tumors and apoptotic state of Ishikawa and HEC-1Acells were tested in vivo using the inhibitory rate, the terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, H/E-stain. Western blot analysis was used to detect the alterations of activated ERK (P-ERK) and AKT (P-AKT) during this process. Results: LY294002, a PI3K/Akt pathway inhibitor, induced significant suppression in the growth of both Ishikawa and HEC-1Acell xenograft tumors, concomitant with increased apoptosis in xenografts as evidenced by TUNEL. A similar effect was also observed when the MAPK/ERK1/2 signaling pathway was inhibited by PD98059. Concurrent inhibition of the PI3K/Akt and MAPK/ERK1/2 pathways showed enhanced anti-tumor effects in vivo as indicated by increased apoptosis. At the same time, the levels of P-ERK and P-AKT in both xenograft tumors decreased, and their levels in combination group was the lowest. Conclusions: PD98059, LY294002 and their combinations showed remarkable inhibitory effects on xenograft tumors of endometrial carcinoma cell lines with different expression status of ER in vivo through blockage of PI3K/Akt and MAPK/ERK1/2 signaling pathways. This suggests that targeting these pathways may be an effective therapeutic strategy against endometrial carcinomas, especially for ER-negative cancers which show poor response to endocrinal therapy.
文摘In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.
基金Supported by Ruian Natural Science Foundation,No.MS2021008.
文摘BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPINH1 in colorectal cancer(CRC)remain largely elusive.AIM To investigate the effects of SERPINH1 on CRC cells and its specific mechanism.METHODS Quantitative real-time polymerase chain reaction,western blotting analysis,The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues.A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC.RESULTS SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues,manifested at both mRNA and protein tiers.Elevated SERPINH1 levels correlated closely with advanced T stage,lymph node involvement,and distant metastasis,exhibiting a significant association with poorer overall survival among CRC patients.Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation,invasion,and migration in vitro,while conversely,SERPINH1 knockdown elicited the opposite effects.Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation.Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation,thereby facilitating CRC cell invasion and migration.CONCLUSION These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC,potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.
