摘要
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.
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 expression 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 expression 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.
出处
《世界华人消化杂志》
CAS
北大核心
2006年第13期1257-1261,共5页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.30271269~~
关键词
胃癌
信号转导通路
增殖
脱嗜作用
Gastric cancer
Signal transductionpathway
Proliferation
Apoptosis