贝母素乙增强阿霉素对胃癌多药耐药裸鼠移植瘤的抑制作用及其机制研究

目的 研究贝母素乙逆转胃癌细胞多药耐药性（MDR），增强化疗药物对胃癌多药耐药裸鼠移植瘤的抑制作用，探讨其作用机制。方法 制备胃癌耐药SGC7901/VCR细胞株裸鼠皮下移植瘤模型，随机分组后，ip给药，每2天给药1次，共给药6次。治疗期间观察裸鼠体质量，游标卡尺测量移植瘤体积。治疗结束后处死裸鼠，称取肿瘤质量，计算抑瘤率；Western blotting检测药物治疗后移植瘤耐药相关蛋白P-糖蛋白（P-gp）、Cleaved Caspase-3表达水平。结果 治疗期间联合用药组移植瘤体积小于模型组，差异显著（P＜0.01）。治疗结束后处死裸鼠，称取移植瘤的质量，联合用药组移植瘤质量和抑瘤率显著低于模型组（P＜0.05）。Western blotting结果显示联合用药组P-gp表达水平较模型组降低，Cleaved Caspase-3表达升高。结论 贝母素乙可以增强胃癌耐药细胞移植瘤对阿霉素的敏感性，能够显著抑制胃癌耐药移植瘤的生长，其机制可能与降低肿瘤组织中P-gp表达和升高Cleaved Caspase-3的表达相关。

Effect of peiminine on enhancing anti-tumor activity of adriamycin on multi-drug resistance of gastric cancer xenografts in nude mice and its mechanism

Objective To investigate the effect of peiminine (PMI) on reversing the multi-drug resistance (MDR) of gastric cancer cell and enhancing the antitumor activity of adriamycin (ADR) on SGC7901/VCR cell xenograft and to explore its functional mechanisms. Methods The model of SGC7901/VCR cell line xenograft on athymic mice was established, and the mice were randomized to groups with ip injection of different drugs once every other day, for six times in all. The tumor volume and the body weight of mice were measured during the drug therapy. The mice were sacrificed after the last administration. The tumors were weighed and then the inhibitory rate was calculated. Western blotting was employed to detect the expression of P-glycoprotein (P-gp) and Cleaved Caspase-3. Results During the treatment, the tumor volume of mice in PMI + ADR group was decreased significantly compared with the control group (P < 0.01). At the end of the treatment the mice were sacrificed and the tumor weight was measured. The tumor weight and inhibitory rate of mice in PMI + ADR group were obviously decreased compared with the control group (P < 0.05). The expression of P-gp in tumor of mice in ADR + PMI group was decreased. On the contrary, the expression of Cleaved Caspase-3 was increased. Conclusion The PMI is able to enhance the sensitivity of drug resistance on gastric cancer cell to adriamycin and its mechanism may be related to decreasing the expression of P-gp and increasing the expression of Cleaved Caspase-3 in tumor tissues.