研究探讨蛋白酶体抑制剂MG132(Z-Leu-leu-leu-CHO)诱导肝癌细胞Hep3B凋亡的作用与机制。实验采用不同浓度梯度和时间梯度,通过荧光显微镜、Hoechst33342染色、MTT检测和Western印迹分别检测MG132对Hep3B细胞的形态、凋亡小体形成、细胞存活率、细胞凋亡相关蛋白表达的影响。结果表明,MG132能够选择性抑制肝癌细胞生长,对正常肝细胞没有明显影响。此外,MG132可以通过内质网应激途径诱导肝癌细胞Hep3B凋亡,呈现剂量和时间的双重依赖性。提示通过抑制蛋白酶体来达到诱导肿瘤细胞凋亡的方法是可行的,MG132此类药物的研究与应用将为肿瘤治疗提供新的选择。
This research investigates the effects of proteasome inhibitor MG132 on human hepatocarcinoma cell Hep3B and its possible mechanism.After being treated with different-concentration of MG132 at different-time,the morphological,formation of apoptotic bodies,cells viability,cell apoptosis and the protein expression involved in the apoptosis signaling pathway in Hep3B cells are assessed by fluorescence microscope,Hoechst33342 staining,MTT assay and Western blotting.Results show that Mg132 can inhibit cell growth in tumor cells but not in normal cells.In addition,It is confirmed that proteasome inhibitor MG132 can induce apoptosis in Hep3B.The mechanism is associated with activation of Caspase-12 via endoplasmic reticulum stress pathway.The effects of MG132 present double manners: concentration and time dependence.These results suggest that hepatocarcinoma cell apoptosis can be induced by proteasome inhibition.The research and application of proteasome inhibitors such as MG132 provide new choice for tumor therapy.