TRAIL联合顺铂对小鼠移植型肝癌抑制作用及机制研究

Inhibitory action and mechanism of trail combined with cisplatin on transplanted hepatocellular carcinoma in mice

目的探讨肿瘤坏死因子相关的凋亡诱导配体(tumor necrosis factor-related apoptosis inducing ligand,TRAIL)联合顺铂(cisplatin,DDP)对小鼠移植型肝癌的抑制作用及机制。方法将H22小鼠移植型肝癌模型随机分为生理盐水组、TRAIL组、TRAIL+DDP组和DDP组,称取瘤重并分析抑瘤率,Hoechst 33342荧光染色法检测细胞凋亡,免疫组织化学染色检测Caspase-3表达。结果与生理盐水组比较,TRAIL、DDP对小鼠移植型肝癌生长具有明显的抑制作用(P<0.05);TRAIL与DDP联合用药具有增效作用(P<0.05),可明显提高肝癌细胞的凋亡率(P<0.05)、上调Caspase-3表达(P<0.01)。结论 TRAIL与DDP联合用药对小鼠移植型肝癌生长具有协同抑制作用,其机制可能与其协同促进Caspase-3的表达有关。

Objective To study the mechanism and the inhibitory action of TRAIL combined with DDP on transplanted hepatocellular carcinoma in mice. Methods Mice bearing H22 hepatocellular carcinoma were randomly divided into normal saline（NS） group,TRAIL group,TRAIL＋DDP group,and DDP group.Tumor tissues were weighted and the inhibitory rate was analysed.Hoechst 33342 stainning method was used to calculate the apoptotic cells.The expression of Caspase-3 was measured by immunohistochemistry. Results Compared with NS,both TRAIL and DDP obviously inhibited the growth of transplanted hepatocellular carcinoma in mice（P0.05）.They had a synergistic effect（P0.05） and obviously increased the apoptotic rate of cancer cells（P0.05）and the expression of Caspase-3（P0.01）. Conclusion The combination of TRAIL with DDP has a synergisticly inhibitory effect on the growth of transplanted hepatocellular carcinoma in mice,and the mechanism may be associated with the synergistic upregulation of Caspase-3 expression.