Stat3反义寡核苷酸联合化疗调控结肠癌细胞增殖与凋亡的分子机制

目的　探讨Stat3反义寡核苷酸 (Stat3AS ON)联合 5 氟尿嘧啶 (5 FU )治疗结肠癌的作用机制。方法　应用Stat3AS ON与 5 FU处理结肠癌细胞HCT116,Westernblot检测Stat3、p Stat3、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　Stat3AS ON与 5 FU作用于HCT116细胞 72h后 ,G1期细胞比率由 63 .7%上升至 82 .2 % ,S期细胞比率分别由 17.6% ,下降至 9.9% ,凋亡细胞百分比由 6.1%增加至 3 2 .0 %。Stat3AS ON与 5 FU可以抑制结肠癌细胞增殖 ,促进结肠癌细胞凋亡 ,联合应用Stat3AS ON与 5 FU可以起协同作用 ,明显抑制结肠癌细胞Stat3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

Molecular mechanisms involved in regulation of proliferation and apoptosis by Stat3 antisense oligonucleotide and chemotherapy in colon cancer cells

Objective To study the mechanism of Stat3 antisense oligonucleotide (Stat3 AN-ON) in combination with 5-FU in the treatment of colon cancer.Methods Stat3 AS-ON,5-FU,or Stat3 AS-ON 5-FU was added into culture media.The expression of Stat3,p-Stat3,Cyclin D1 and bcl-xL was detected by Western blot.The cell proliferation was assayed by MTT.Flow cytometry was performed to analyze the cell cycle and apoptosis.Results After the treatment of HCT116 cells with Stat3 AS-ON and 5-FU for 72 h,the ratio of G 1 phase was up-regulated from 63.7% to 82.2%,while that of S phase was down-regulated from 17.6% to 9.9%,and the percentage of apoptotic cell was increased from 6.1% to 32.0%.Stat3 AS-ON and 5-FU could suppress the growth of colon cancer cells and induce significant apoptosis of colon cancer cells.Combined use of them has a synergic effect,obviously inhibiting the activation of Stat3 signaling tranduction pathway of colon cancer cells.Conclusion Selective inhibition of specific signaling pathway may provide a new therapeutic approach for treating colon cancers.