索拉非尼与顺铂的不同联合方案对肝癌HepG2细胞的作用研究

摘要：目的 探讨索拉非尼（Sorafenib，BAY 43-9006，Nexavar）联合顺铂（cisplatin，DDP）对肝癌细胞HepG2的杀伤作用。方法 单独、同时及序贯联合给药后以MTT法测定HepG2细胞的增殖，用流式细胞仪检测细胞凋亡。结果 索拉非尼及DDP单药对HepG2均有抑制作用，两药同时给药具有协同或相加作用（P<0. 05）。序贯用药DDP先用组与同时给药组相比疗效相似（P>0. 05），表现为协同或相加作用。而索拉非尼先用组疗效差于前两者(P<0. 05)，显示拮抗作用。联合用药组凋亡率均比单药组高（P<0. 05），同时给药组及DDP先用组凋亡率比索拉非尼先用组高（P<0. 05，P<0. 05）。结论　索拉非尼和顺铂对肝癌HepG2细胞有增殖抑制及促凋亡作用，同时给药表现为协同或相加作用，序贯联合用药产生单向协同或相加作用。

Sorafenib and cisplatin of different combination modalities inhibit cell proliferation in hepatocellular carcinoma cells HepG2

Objective To investigate the killing effect of sorafenib (BAY 43-9006, Nexavar) in combination with cisplatin (DDP) on hepatocellular carcinoma cell line HepG2. Methods The proliferation of HepG2 cells was determined by MTT assay and the apoptotic rate was detected by flow cytometry after administration with sorafenib alone or in combination with DDP. Results Either sorafenib or DDP had an inhibitory effect on HepG2 cells and sorafenib plus DDP revealed a synergistic or additive effect (P < 0.05). The efficacy in the patients receiving sequential chemotherapy with DDP and sorafenib was similar to that in those receiving sorafenib plus DDP(P > 0.05), showing a synergistic or additive effect. However, the efficacy in those receiving sorafenib followed by DDP was worse than that in the former two therapies, revealing an antagonistic effect (P < 0.05). The apoptotic rate was higher in the dual-therapy group than in the monotherapy groups (P < 0.05) and higher in the patients receiving sequential therapy with DDP and sorafenib or sorafenib plus DDP than those receiving sorafenib following by DDP (P < 0.05). Conclusions Sorafenib or DDP alone has an inhibitory effect on the proliferation of HepG2 cells and induces apoptosis of the cells. Simultaneous administration with sorafenib and DDP has a synergistic or additive effect and sequential chemotherapy reveals a unidirectional synergistic or additive effect.