Gamma-tocotrienol,a member of vitamin E superfamily has attracted great attention of late for its anti-proliferative and anti-carcinogenic potential against different cancers.For example,our group had previously repor...Gamma-tocotrienol,a member of vitamin E superfamily has attracted great attention of late for its anti-proliferative and anti-carcinogenic potential against different cancers.For example,our group had previously reported that anti-proliferative and chemosensitizing effects ofγ-tocotrienol are associated with its ability to suppress activation of signal transducers and activator of transcription 3(STAT3),apro-inflammatory transcription factor that plays a pivotal role in the survival,proliferation,angiogenesis and chemoresistance of hepatocellular carcinoma.However,the potential of gamma-tocotrienol to overcome chemoresistance in gastric cancer,which is one of the deadliest cancers in Asia-pacific region,has never been explored before.Hence,we analyzed the efficacy of gamma-tocotrienol in combination with capecitabine to modulate tumor growth and survival in gastric cancer cell lines and xenograft mouse model.Cell proliferation and apoptosis assays indicated that gamma-tocotrienol potentiated capecitabine induced programmed cell death in various gastric cancer cell lines.Gamma-tocotrienol also inhibited expression of Bcl-2,Bcl-xL,cyclin-D1,COX-2,ICAM-1,VEGF,CXCR4,MMP-9 proteins,induced PARP cleavage and inhibited constitutive and capecitabine-induced NF-κB activation in gastric cancer cells.In vivo studies using xenograft model of human gastric cancer demonstrated that gamma-tocotrienol alone suppressed tumor growth and this effect was further potentiated in conjunction with capecitabine.Also the markers of proliferation index Ki-67 and the micro vessel density CD31 were significantly downregulated in tumor tissues by the combination of capecitabine and gamma-tocotrienol.As compared to the vehicle control,gamma-tocotrienol further suppressed the NF-κB activation and expression of cyclin D1,COX-2,ICAM-1,MMP-9 and survivin in tumor tissues obtained from treatment groups.Overall our results suggest for the first time that gamma-tocotrienol can potentiate the effects of capecitabine through modulation of multiple markers of proliferation,invasion,angiogenesis and metastasis in gastric cancer.展开更多
文摘Gamma-tocotrienol,a member of vitamin E superfamily has attracted great attention of late for its anti-proliferative and anti-carcinogenic potential against different cancers.For example,our group had previously reported that anti-proliferative and chemosensitizing effects ofγ-tocotrienol are associated with its ability to suppress activation of signal transducers and activator of transcription 3(STAT3),apro-inflammatory transcription factor that plays a pivotal role in the survival,proliferation,angiogenesis and chemoresistance of hepatocellular carcinoma.However,the potential of gamma-tocotrienol to overcome chemoresistance in gastric cancer,which is one of the deadliest cancers in Asia-pacific region,has never been explored before.Hence,we analyzed the efficacy of gamma-tocotrienol in combination with capecitabine to modulate tumor growth and survival in gastric cancer cell lines and xenograft mouse model.Cell proliferation and apoptosis assays indicated that gamma-tocotrienol potentiated capecitabine induced programmed cell death in various gastric cancer cell lines.Gamma-tocotrienol also inhibited expression of Bcl-2,Bcl-xL,cyclin-D1,COX-2,ICAM-1,VEGF,CXCR4,MMP-9 proteins,induced PARP cleavage and inhibited constitutive and capecitabine-induced NF-κB activation in gastric cancer cells.In vivo studies using xenograft model of human gastric cancer demonstrated that gamma-tocotrienol alone suppressed tumor growth and this effect was further potentiated in conjunction with capecitabine.Also the markers of proliferation index Ki-67 and the micro vessel density CD31 were significantly downregulated in tumor tissues by the combination of capecitabine and gamma-tocotrienol.As compared to the vehicle control,gamma-tocotrienol further suppressed the NF-κB activation and expression of cyclin D1,COX-2,ICAM-1,MMP-9 and survivin in tumor tissues obtained from treatment groups.Overall our results suggest for the first time that gamma-tocotrienol can potentiate the effects of capecitabine through modulation of multiple markers of proliferation,invasion,angiogenesis and metastasis in gastric cancer.
