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

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

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。

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.