亚硒酸钠对肝癌细胞发生自噬的影响_图文.pptVIP

自噬模式图 自噬及凋亡的关系 1．自噬抑制凋亡：自噬通过降解受损蛋白损伤等途径抑制凋亡。 2．自噬促进凋亡：自噬自身并不引起细胞死亡，但它为凋亡小体的形成和吞噬作用提供能量，从而促进凋亡的发生。 3．自噬与凋亡共存并可相互转换：在自噬晚期使用特异性自噬抑制剂则使自噬性死亡转向凋亡，有文献报道imatinib可以致恶性神经胶质瘤细胞发生自噬性死亡，然而在自噬晚期使用自噬抑制剂可使自噬性死亡转向凋亡，而当细胞凋亡被抑制剂阻断细胞则转向自噬，此时不论抑制凋亡还是自噬，细胞均转变为另一条途径的细胞死亡。 自噬对肿瘤的双重作用 （1）统计数据用SPSS20.0 软件包进行分析。 （2）实验数据均以均数±标准差表示。 （3）采用单因素方差分析。 （1）成功建立人肝癌细胞索菲拉尼耐药株鼠移植瘤的动物模型 （2）需继续查阅大量文献确定小鼠灌胃给药浓度及剂量; （3）熟练掌握干预动物给药方式。 （4）检测各个指标的实验技术方法需熟练掌握； * Sorafenib Blocks the RAF/MEK/ERK Pathway, Inhibits Tumor Angiogenesis, and Induces Tumor Cell Apoptosis in Hepatocellular Carcinoma Model PLC/PRF/5 Angiogenesis and signaling through the RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development ofhep atocellular carcinomas (HCC). Sorafenib (BAY 43-9006, Nexavar) is a multikinase inhibitor with activity against Rafkin ase and several receptor tyrosine kinases, including vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), FLT3, Ret, and c-Kit. In this study, we investigated the in vitro effects of sorafenib on PLC/PRF/5 and HepG2 HCC cells and the in vivo antitumor efficacy and mechanism of action on PLC/ PRF/5 human tumor xenografts in severe combined immunodeficient mice. Sorafenib inhibited the phosphorylation of MEK and ERK and down-regulated cyclin D1 levels in these two cell lines. Sorafenib also reduced the phosphorylation level of eIF4E and down-regulated the antiapoptotic protein Mcl-1 in a MEK/ ERK–independent manner. Consistent with the effects on both MEK/ERK–dependent and MEK/ERK–independent signaling pathways, sorafenib inhibited proliferation and induced apoptosis in both HCC cell lines. In the PLC/PRF/5 xenograft model, sorafenib tosylate dosed at 10 mg/kg inhibited tumor growth by 49%. At 30 mg/kg, sorafenib tosylate produced complete tumor growth inhibition. A dose of100 mg/kg produced partial tumor regressions in 50% o