TRAIL联合顺铂诱导肝癌细胞HepG2凋亡的研究

目的 探讨顺铂增加TRAIL诱导肝癌细胞HepG2凋亡的分子机制，提供TRAIL应用肝癌临床治疗的一种新的用药模式。方法 以肝癌细胞HepG2为研究对象，应用流式细胞仪分析顺铂联合应用TRAIL对细胞周期的影响，Western blot检测顺铂作用前后HepG2细胞在TRAIL诱导凋亡过程中Caspase-8、Caspase-3、DR4、DR、DcR，c—FLIP及RIP的表达变化。结果 顺铂能够增强TRAIL诱导HepG2细胞凋亡的能力，两者联合应用具有明显的协同作用，顺铂预先处理能够下调c-FLIP及RIP的表达及增加DR的表达。结论 TRAIL联合顺铂可以诱导肝癌细胞HepG2凋亡，其机制是通过下调c-FLIP及RIP的表达，解除Caspase-8受抑，恢复凋亡信号的传导来实现的。死亡受体D＆的表达上调也可能参与了这一变化过程。

Experimental study on the induction of HepG2 cell apoptosis induced by cispaltin in combination with TRAIL

Objective To investigate the synergistic molecular mechanism of Cisplatin enhancing the TRAIL-induced apoptosis of hepatocellular carcinoma HepG2 cell lines and provide a novel treatment model of the TRAIL in HCC. Methods The HepG2 cells cycle co-treated with Cisplatin and TRAIL was analyzed by flow cytometry, and the expression of signal transduction proteins, such as Caspase-8, Caspase- 3, DR4, DR5, DcR1 , c-FLIP and RIP was detected by Western blot before and after the treatment of Cisplatin. Results Pretreatment with lower dose of Cisplatin could reverse the sensitivity of HepG2 cells to TRAIL-induced apoptosis, and could down-regulate the expression of c-FLIP and RIP, up-regulate the expression of DR5. Conclusion Cisplatin could sensitize HepG2 cells to TRAIL-induced apoptosis, which might be contributed to the down-regulation of the expression of c-FLIP and RIP, reversal of the inhibition of Caspase-8 and the up-regulation of DR5.