氯喹通过诱导凋亡增强5-氟尿嘧啶的抗结肠癌效果

Chloroquine Enhances the Antitumor Effect of 5-fluorouracil on Colon Cancer through Inducing Apoptosis

目的:探讨结肠癌化疗药物5-氟尿嘧啶(5-fluorouracil,5-FU)与各个阶段的自噬抑制剂联合使用后,结肠癌细胞的增殖和凋亡情况,以寻找合适的治疗结肠癌的药物。方法:自噬三个阶段的抑制剂与5-FU联合使用处理结肠癌细胞系HT-29和SW480后,MTT方法检测细胞增殖情况,流式细胞术检测细胞凋亡情况,western blot检测细胞自噬和凋亡情况。结果:5-FU能诱导结肠癌细胞的自噬和凋亡。3-甲基腺嘌呤(3 methyladenine,3-MA)和氯喹(Chloroquine,CQ)均能增强5-FU诱导的结肠癌细胞凋亡,而CQ的增强效果更加明显。同时,又进一步证明了CQ可诱导结肠癌细胞发生caspase依赖的结肠癌细胞凋亡。结论:CQ有望成为一种能与5-FU联合使用治疗结肠癌的有效化疗药物。

Objective To investigate the effects of 5-fluorouracil（ 5-FU） combined with autophagy inhibitors in various stages on proliferation and apoptosis of colon cancer cells thereby finding a suitable drug for colon cancer. Methods HT29 and SW480 cells were treated with the combined use of autophagy inhibitors in three stages with 5-FU. The proliferation rate of cancer cells was analyzed by MTT assay. Apoptosis was quantified by flow-cytometry after the cells were double-stained with Annexin V/PI. Autophagy and apoptosis were further confirmed by western blot analysis. Results Our results demonstrated that 5-FU could induce apoptosis and autophagy in colon cancer cells. Both 3-MA and CQ could enhance the apoptosis induced by 5-FU in colon cancer cells,while CQ had better inhibitory effect against the proliferation of colon cancer cells. Meanwhile,CQ could induce a caspase-dependent apoptosis in colon cancer cells. Conclusion Based on the above results,we proposed that the combined use of 5-FU with CQ is expected to become a novel therapeutic method for the treatment of colon cancer.