目的：研究蛋白酶体抑制剂MG132抑制胆囊癌细胞增殖及诱导凋亡的机制。方法采用CCK8和流式细胞术检测胆囊癌细胞增殖及凋亡情况；采用Westernblotting和RT-PCR检测凋亡相关基因Caspase-8、Caspase-3和DR5的mRNA和蛋白质表达；建立荷瘤裸鼠模型，观察MG132干预下裸鼠瘤重及瘤体积的变化。结果在本研究中发现MG132能有效抑制体外和体内胆囊癌细胞的增殖，其作用呈剂量依赖性（P＜0.01）。MG132能促使胆囊癌细胞发生G2/M期阻滞及诱导细胞凋亡。MG132诱导胆囊癌细胞凋亡主要通过激活外源性凋亡通路中DR5、Caspase-8和Caspase-3过表达。结论 MG132能对胆囊癌细胞起杀伤作用，其机制可能通过影响细胞周期阻滞及诱导细胞凋亡起作用。%objective To investigate the mechanism of proteasome inhibitor MG132 in inhibiting prolifera-tion and inducing apoptosis of gallbladder cancer cells. Methods The anti-tumor activity of MG132 on gallblad-der cancer cells was assessed by the CCK8 assay. Apoptosis changes were detected by flow cytometric analysis. The protein and mRNA expression of Caspase-8, Caspase-3 and DR5 were examined using Western blotting and RT-PCR. Gallbladder cancer xenografts in athymic nude mice were established and the tumor weight and volume were measured after the intervention of MG132. Results The results showed that MG132 inhibited the prolifera-tion of gallbladder cancer cells in a dose-dependent manner both in vivo and in vitro (P<0.01). Exposure of tumor cells to MG132 induced cell cycle arrest at G2/M phase and apoptosis in a dose- dependent manner (P<0.01). In addition, analysis of apoptotic pathways indicated that MG132 significantly enhanced the activation of Caspase-8, Caspase-3 and DR5 in extrinsic signaling pathway (P<0.05). Conclusion Proteasome inhibitor MG132 can ef-fectively kill gallbladder cancer cells and its mechanism involves the cell cycle arrest and apoptosis induction.
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