Stat5反义寡核苷酸联合Jak激酶抑制剂AG490调控结肠癌细胞增殖与凋亡的分子机制

Molecular Mechanisms Involved in Regulation of Proliferation and Apoptosis by Stat5 Antisense Oligonucleotide and AG490 in Colon Cancer Cells

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。

Abstract: Objective In this study, we show that inhibition of the Stat5 signaling pathway using Stat5 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. Result...