摘要
目的探讨Stat5反义寡核苷酸(Stat5AS-ON)联合Jak激酶抑制剂(AG490)治疗结肠癌的作用机制。方法应用Stat5AS-ON与AG490处理结肠癌细胞HT29,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AG490作用于HT29细胞72h后,G1期细胞比率由72.7%上升至87.2%,S期细胞比率分别由19.6%,下降至7.5%,凋亡细胞百分比由8.7%增加至24.2%。Stat5AS-ON与AG490可以抑制结肠癌细胞增殖,促进结肠癌细胞凋亡,联合应用Stat5AS-ON与AG490可以起协同作用,明显抑制结肠癌细胞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结肠癌提供新途径。
Objective In this study, we show that inhibition of the Star5 signaling pathway using Star5 AS-ON and AG490 significantly suppress the growth of colon cancer cell lines harboring constitutive active Stat5. Methods Stat5 AS ON, AG490, or Stat5 AS-ON ＋ AG490 was added into culture media, followed by MTT assay, the absorption value was measured and the growth curve was drawn; western blot analysis was performed on colon cancer cell lines; flow cytometry was applied to analyze the cell cycle and apoptosis. Results After the treatment of HT29 cells with Star5 AS-ON and AG490 for 72h, the ratio of G1 phase was up-regulated from 72.7% to 87. 2%, S phase was down-regulated from 19. 6% to 7. 5%, and the percentage of apoptotic cell was increased from 8. 7% to 24. 2%. Star5 AS-ON and AG490 could suppress the growth of colon cancer cells, they also induced significant apoptosis in colon cancer cells, and they diminished the expression and phosphorylation of Star5, also the expression of cyclin D1 and Bcl -xL. Conclusion These results suggest that selective inhibition of specific signaling pathway may provide a new therapeutic approach for treating colon cancers.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2006年第12期883-886,共4页
Cancer Research on Prevention and Treatment
基金
国家自然科学基金资助项目(30271269)
关键词
结肠癌
信号转导
增殖
脱嗜作用
Colon neoplasm
Signal transduction
Proliferation
Apoptosis
