PHA-767491联合TRAIL抑制肝癌细胞Bel-7404增殖

将小分子抗癌药物PHA-767491和携带TRAIL基因的非复制型腺病毒(Ad-TRAIL)共同作用于肝癌细胞Bel-7404，探讨PHA-767491联合TRAIL蛋白对肝癌细胞增殖的协同抑制作用及其作用机理. MTT法检测细胞存活率,Hoechst 33342荧光检测细胞凋亡现象和流式细胞仪检测细胞凋亡水平. 结果表明，PHA-767491联合Ad-TRAIL抑制Bel-7404细胞增殖的能力显著优于单一用药. Western印迹进一步分析蛋白表达水平显示，PHA-767491可以通过下调抗凋亡蛋白Mcl-1和Xiap的表达，从而显著增强TRAIL蛋白诱导Bel-7404细胞凋亡的能力；PHA-767491联合Ad-TRAIL处理Bel-7404细胞后，不仅Bel-7404细胞凋亡水平显著增加，并且伴随着PARP和Caspase3的大量剪切. 本研究证实, PHA-767491和TRAIL的联合使用对抑制肝癌细胞Bel-7404增殖表现出了显著的协同效应，为今后癌症药物的联合治疗提供了新的思路.

Combination of PHA-767491 with TRAIL Inhibits Proliferation of Hepatocellular Carcinoma Bel-7404 Cells

To explore the coordinating repression to hepatocellular carcinoma cell proliferation by PHA-767491 combining TRAIL and the inhibiting mechanism, small molecule anti-cancer drug PHA-767491 and replication-deficient adenoviral vector carrying TRAIL (Ad-RAIL) were used jointly to work on Bel-7404 cell. By testting cell survival rate by MTT and observing apoptosis phenomenon via Hoechst 33342 fluorescence staining and apoptosis level by flow cytometry, the results showed that combining PHA-767491 with Ad-TRAIL promoted the growth inhibition of Bel-7404 cell compared with either PHA-767491 or Ad-TRAIL alone. Western blots analysis showed that PHA-767491 enhanced to induce apoptosis of TRAIL by down-regulating Mcl-1 and Xiap expression; PHA-767491 combined with Ad-TRAIL induced remarkable apoptosis and cleavage of caspase 3 and PARP in Bel-7404 cells. In conclusion, combination therapy of PHA-767491 and TRAIL exerted a synergistic anti-tumor effect on Bel-7404 cells, it will provide a new idea for combined treatment of cancer.