Stat5反义寡核苷酸联合5-氟尿嘧啶对胃癌细胞增殖与凋亡的影响

目的:探讨Stat5反义寡核苷酸(Stat5AS-ON)联合5-氟尿嘧啶(5-FU)治疗胃癌的作用机制.方法:Stat5AS-ON、5-FU单用或联用处理胃癌细胞BGC823,Westernblot检测Stat5、p-Stat5、cyclinD1与Bcl-xL表达,MTT法检测细胞增殖状态,流式细胞技术检测细胞周期与凋亡.结果:Stat5AS-ON与5-FU作用于BGC823细胞72h后,G1期细胞比率由65.7%上升至78.2%,S期细胞比率分别由18.6%,下降至10.5%,凋亡细胞百分比由7.4%增加至21.6%.Stat5AS-ON与5-FU可以抑制胃癌细胞增殖,促进胃癌细胞凋亡,联合应用Stat5AS-ON与5-FU可以起协同作用,明显抑制胃癌细胞Stat5信号转导通路活化.结论:选择性阻断细胞内信号转导通路可能为治疗胃癌提供新途径.

Effects of Stat5 antisense oligonucleotide combined with 5-fluorouracil on proliferation and apoptosis of gastric cancer cells

AIM: To investigate the mechanism of Stat5 antisense oligonucleotide (Stat5 AS-ON) combined with 5-fluorouracil (5-FU) in the treatment of gastric cancer. METHODS: Human gastric cancer cell line BGC823 was treated with Stat5 AS-ON and 5-FU, respectively, or in combination. The ex- pression of Stat5, p-Stat5, cyclin D1 and Bcl-xL in the cells were detected by Western blot, and the cell cycle and apoptosis were detected by flow cytometry. RESULTS: After treatment with Stat5 AS-ON and 5-FU for 72 h, the ratio of G1-phase cells was up-regulated from 65.7% to 78.2%, and that of S-phase cells was down-regulated from 18.6% to 10.5%; the percentage of apoptotic cells was increased from 7.4% to 21.6%. Stat5 AS-ON and 5-FU synergically inhibited the growth of gastric cancer cells, induced significant apoptosis of the cancer cells, and they reduced the expression and phosphorylation of Stat5, as well as the ex- pression of cyclin D1 and Bcl-xL. CONCLUSION: Selective inhibition of specific signaling pathway in the cells may provide a new approach in the treatment of gastric cancer.