β-elemene has been observed to exert inhibitory effects on a multitude of tumors,primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis.The present stud...β-elemene has been observed to exert inhibitory effects on a multitude of tumors,primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis.The present study is designed to elucidate the role and underlying mechanisms ofβ-elemene in the therapeutic intervention of non-small cell lung cancer(NSCLC).Both in vitro and in vivo experimental models corroborate the inhibitory potency ofβ-elemene on NSCLCs.Our findings indicate thatβ-elemene facilitates the maturation of miR-127-3p by inhibiting CBX8.Functioning as an upstream regulator of MAPK4,miR-127-3p deactivates the Akt/mTOR/p70S6K pathway by targeting MAPK4,thereby inducing autophagy in NSCLCs.Additionally,β-elemene augments the packaging of miR-127-3p into exosomes via SYNCRIP.Exosomal miR-127-3p further stimulates M1 polarization of macrophages by suppressing ZC3H4.Taken together,the detailed understanding of the mechanisms through whichβ-elemene induces autophagy in NSCLCs and facilitates M1 polarization of macrophages provides compelling scientific evidence supporting its potential utility in NSCLC treatment.展开更多
Objective： To explore the effect and possible mechanism in vitro of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung. Methods： The A549 cell line from adenocarcinoma of lung was chosen ...Objective： To explore the effect and possible mechanism in vitro of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung. Methods： The A549 cell line from adenocarcinoma of lung was chosen for the study to determine the inhibition ratio by using MTT assay. Morphologic change, growth curve, cloning efficiency, divisional index were observed. Change of cell cycle and apoptosis rate were analyzed by FCM and the expressions of gene P53 and Bcl-2 were detected. Results： Reproductive activity of the group which was under irradiation and β-Elemene was significantly suppressed and its cloning efficiency and divisional index also declined. The apoptosis rate of the group which was under irradiation and β-Elemene was significantly higher at 48 h and 72 h, which was analyzed by FCM. The expression of P53 without Bcl-2 was observed in the group under irradiation and β-Elemene and the group under β-Elemene only at the 48th hour point, while the expression of Bcl-2 without p53 was observed in the group under irradiation only and the control group. Conclusion： β-Elemene is good at radiosensitization and its mechanism may be relevant to the up-regulation of P53, down-regulation of Bcl-2 and inducing apoptosis.展开更多
AIM:To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms.METHODS:SGC7901,MKN45,MKN28,N87,and AGS human gastric cancer cell lines were used to screen for ra...AIM:To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms.METHODS:SGC7901,MKN45,MKN28,N87,and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium(MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death,respectively. A proteomic method,isobaric tags for relative and absolute quantitation(i TRAQ),was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation(IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1(Pak1) to target Pak1 signaling. Protein levels of PAK1IP1(p21-activated protein kinase-interacting protein 1),total Pak1(t-Pak1),phospho-Pak1(T423),phospho-ERK1/2( Thr202/Tyr204),and cleaved caspase-3(17 k Da) were assessed by western blotting.RESULTS:MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally,β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45(10.4% ± 0.9% vs 34.8% ± 2.8%,P < 0.05) and SGC7901(11.6% ± 0.9% vs 46.7% ± 5.2%,P < 0.05) human gastric cancer cell lines,respectively,consistent with the level of cleaved caspase-3(17 k Da). Through i TRAQ analysis and western blot validation,we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1(T423) and phosphoERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1(T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition,IPA-3 increased radiation-induced cell death in MKN45(13.4% ± 0.3% vs 26.6% ± 1.0%,P < 0.05) and SGC7901(16.0% ± 0.6% vs 37.3% ± 1.7%,P < 0.05) gastric cancer cell lines,respectively,consistent with the level of cleaved caspase-3(17 k Da). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation.CONCLUSION:This is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells,and that the mechanism involves inhibition of Pak1 signaling.展开更多
Objective： To investigate the impact of beta-elemene injection on the growth and alpha-tubule of human hepatocarcinoma HepG2 cells. Methods： Cell proliferation was assessed by MTT assay. Cell cycle distribution was ...Objective： To investigate the impact of beta-elemene injection on the growth and alpha-tubule of human hepatocarcinoma HepG2 cells. Methods： Cell proliferation was assessed by MTT assay. Cell cycle distribution was detected by flow cytometry （FCM）. The mRNA expression of alpha-tubulin was measured by RT-PCR. Western blot analysis was used to determine protein expression of alpha-tubulin and the polymerization of tubulin. Results： Beta-elemene injection inhibited HepG2 cells proliferation in a dose- and time-dependent manner; FCM analysis indicated beta-elemene injection induced cell cycle arrested at S phase. RT-PCR and western- blot analysis showed that beta-elemene injection down-regulated alpha-tublin at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. Conclusions： Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells and induce cell apoptosis, the mechanism might be partly related to the down-regulation of alpha-tubulin and inhibition of microtubular polymerization.展开更多
To investigate the effects of β-elemene on the ANG Ⅱ-ATI receptor pathway in rats with liver fibrosis, a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride （CC14） into Wistar m...To investigate the effects of β-elemene on the ANG Ⅱ-ATI receptor pathway in rats with liver fibrosis, a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride （CC14） into Wistar male rats. D-elemene was intraperitonealy administered into the rats for 8 weeks （0.1 mL/100 g body weight per day）. Masson staining was used to observe the liver fibrosis of rats and liver functions were measured by enzymatic kinetic analysis. The content of hydroxyproline in liver tissues was detected by specimen alkaline hydrolysis. The level of plasma ANG Ⅱ in blood plasma was detected by radioimmunoassay. The expression of AT1R in rat liver were measured using reverse transcriptional-polymerase chain reaction and immunohistochemistry respectively. The results showed that β-elemene could reduce the collagen disposition in liver and inhibit the progression of liver fibrosis. In addition, the levels of plasma ANG Ⅱ and the expression of hepatic AT1R in rats with liver fibrosis were also suppressed by β-elemene. It is concluded that the ANG Ⅱ-AT1 receptor pathway plays an important role in the development of hepatic fibrosis and D-elemene could down-regulate the levels of plasma ANG Ⅱ and the expression of hepatic ATIR in rats with liver fibrosis.展开更多
AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced d...AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat model.METHODS: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry methods.RESULTS: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P<0.05). The inhibitory effect of intravitreal injection was more remarkable.CONCLUSION: The results show β-elemene protect the retina of diabetic rats from high glucose damage by downregulating the expression of HIF-1α, VEGF and iNOS.展开更多
Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experime...Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experimental rabbits were divided into three groups: the control group, the radiation group, and the radiation +β-elemene (radiosensitivity) group. The change of tumor was observed by Spiral CT and B ultrasound to compare its regrowth period. The tumor was measured by light microscopy and electron microscopy. Results The tumor in radiosensitivity group was restrained obviously and the sensitization enhancement ratio (SER) of β-elemene was 1.89. Different apoptosis was observed under transmission electron microscopy. Conclusion Low dosage β-elemene can enhance the radiosensitivity of rabbit VX2 renal transplant carcinoma model and induce the apoptosis of tumor cells, but the mechanism needs further study. It promotes apoptosis in mechanisms in vitro.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:81973525)Traditional Chinese Medicine Development Project of Jiangsu Province(Grant No.:ZT202112).
文摘β-elemene has been observed to exert inhibitory effects on a multitude of tumors,primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis.The present study is designed to elucidate the role and underlying mechanisms ofβ-elemene in the therapeutic intervention of non-small cell lung cancer(NSCLC).Both in vitro and in vivo experimental models corroborate the inhibitory potency ofβ-elemene on NSCLCs.Our findings indicate thatβ-elemene facilitates the maturation of miR-127-3p by inhibiting CBX8.Functioning as an upstream regulator of MAPK4,miR-127-3p deactivates the Akt/mTOR/p70S6K pathway by targeting MAPK4,thereby inducing autophagy in NSCLCs.Additionally,β-elemene augments the packaging of miR-127-3p into exosomes via SYNCRIP.Exosomal miR-127-3p further stimulates M1 polarization of macrophages by suppressing ZC3H4.Taken together,the detailed understanding of the mechanisms through whichβ-elemene induces autophagy in NSCLCs and facilitates M1 polarization of macrophages provides compelling scientific evidence supporting its potential utility in NSCLC treatment.
文摘Objective： To explore the effect and possible mechanism in vitro of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung. Methods： The A549 cell line from adenocarcinoma of lung was chosen for the study to determine the inhibition ratio by using MTT assay. Morphologic change, growth curve, cloning efficiency, divisional index were observed. Change of cell cycle and apoptosis rate were analyzed by FCM and the expressions of gene P53 and Bcl-2 were detected. Results： Reproductive activity of the group which was under irradiation and β-Elemene was significantly suppressed and its cloning efficiency and divisional index also declined. The apoptosis rate of the group which was under irradiation and β-Elemene was significantly higher at 48 h and 72 h, which was analyzed by FCM. The expression of P53 without Bcl-2 was observed in the group under irradiation and β-Elemene and the group under β-Elemene only at the 48th hour point, while the expression of Bcl-2 without p53 was observed in the group under irradiation only and the control group. Conclusion： β-Elemene is good at radiosensitization and its mechanism may be relevant to the up-regulation of P53, down-regulation of Bcl-2 and inducing apoptosis.
基金Supported by National Nature Science Foundation of China,No.81172357
文摘AIM:To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms.METHODS:SGC7901,MKN45,MKN28,N87,and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium(MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death,respectively. A proteomic method,isobaric tags for relative and absolute quantitation(i TRAQ),was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation(IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1(Pak1) to target Pak1 signaling. Protein levels of PAK1IP1(p21-activated protein kinase-interacting protein 1),total Pak1(t-Pak1),phospho-Pak1(T423),phospho-ERK1/2( Thr202/Tyr204),and cleaved caspase-3(17 k Da) were assessed by western blotting.RESULTS:MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally,β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45(10.4% ± 0.9% vs 34.8% ± 2.8%,P < 0.05) and SGC7901(11.6% ± 0.9% vs 46.7% ± 5.2%,P < 0.05) human gastric cancer cell lines,respectively,consistent with the level of cleaved caspase-3(17 k Da). Through i TRAQ analysis and western blot validation,we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1(T423) and phosphoERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1(T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition,IPA-3 increased radiation-induced cell death in MKN45(13.4% ± 0.3% vs 26.6% ± 1.0%,P < 0.05) and SGC7901(16.0% ± 0.6% vs 37.3% ± 1.7%,P < 0.05) gastric cancer cell lines,respectively,consistent with the level of cleaved caspase-3(17 k Da). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation.CONCLUSION:This is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells,and that the mechanism involves inhibition of Pak1 signaling.
基金The General Program of National Natural Science Foundation of China:Research Fund for the mechanism of Arenobufagin space isomer inhibits lymphatic metastasis of mouse hepatocarcinomaThe Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education MinistrySpecialized Research Fund for the Doctoral Program of Higher Education(NO.20102105120002)
文摘Objective： To investigate the impact of beta-elemene injection on the growth and alpha-tubule of human hepatocarcinoma HepG2 cells. Methods： Cell proliferation was assessed by MTT assay. Cell cycle distribution was detected by flow cytometry （FCM）. The mRNA expression of alpha-tubulin was measured by RT-PCR. Western blot analysis was used to determine protein expression of alpha-tubulin and the polymerization of tubulin. Results： Beta-elemene injection inhibited HepG2 cells proliferation in a dose- and time-dependent manner; FCM analysis indicated beta-elemene injection induced cell cycle arrested at S phase. RT-PCR and western- blot analysis showed that beta-elemene injection down-regulated alpha-tublin at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. Conclusions： Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells and induce cell apoptosis, the mechanism might be partly related to the down-regulation of alpha-tubulin and inhibition of microtubular polymerization.
基金supported by a grant from the National Natural Sciences Foundation of China (No.30500658)
文摘To investigate the effects of β-elemene on the ANG Ⅱ-ATI receptor pathway in rats with liver fibrosis, a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride （CC14） into Wistar male rats. D-elemene was intraperitonealy administered into the rats for 8 weeks （0.1 mL/100 g body weight per day）. Masson staining was used to observe the liver fibrosis of rats and liver functions were measured by enzymatic kinetic analysis. The content of hydroxyproline in liver tissues was detected by specimen alkaline hydrolysis. The level of plasma ANG Ⅱ in blood plasma was detected by radioimmunoassay. The expression of AT1R in rat liver were measured using reverse transcriptional-polymerase chain reaction and immunohistochemistry respectively. The results showed that β-elemene could reduce the collagen disposition in liver and inhibit the progression of liver fibrosis. In addition, the levels of plasma ANG Ⅱ and the expression of hepatic AT1R in rats with liver fibrosis were also suppressed by β-elemene. It is concluded that the ANG Ⅱ-AT1 receptor pathway plays an important role in the development of hepatic fibrosis and D-elemene could down-regulate the levels of plasma ANG Ⅱ and the expression of hepatic ATIR in rats with liver fibrosis.
文摘AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat model.METHODS: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry methods.RESULTS: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P<0.05). The inhibitory effect of intravitreal injection was more remarkable.CONCLUSION: The results show β-elemene protect the retina of diabetic rats from high glucose damage by downregulating the expression of HIF-1α, VEGF and iNOS.
基金This work was supported by the National Natural Science Foundation of China (No30371831)
文摘Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experimental rabbits were divided into three groups: the control group, the radiation group, and the radiation +β-elemene (radiosensitivity) group. The change of tumor was observed by Spiral CT and B ultrasound to compare its regrowth period. The tumor was measured by light microscopy and electron microscopy. Results The tumor in radiosensitivity group was restrained obviously and the sensitization enhancement ratio (SER) of β-elemene was 1.89. Different apoptosis was observed under transmission electron microscopy. Conclusion Low dosage β-elemene can enhance the radiosensitivity of rabbit VX2 renal transplant carcinoma model and induce the apoptosis of tumor cells, but the mechanism needs further study. It promotes apoptosis in mechanisms in vitro.
