Stat3与过氧化物酶体增殖因子激活受体δ信号转导通路间交互作用对结肠癌细胞增殖的调控影响

Molecular mechanism of cross-talk between signal transducer and activator of transcription 3 and perioxisome proliferators-activated receptor 5 signaling pathway in regulating proliferation of colon cancer cells

目的观察选择性环氧合酶(COX)-2抑制剂NS-398对结肠癌细胞系SW480中 Stat3与过氧化物酶体增殖因子激活受体(PPAR)δ信号转导通路的影响,探讨不同信号转导通路间交互作用调控结肠癌细胞增殖的分子机制。方法应用逆转录-聚合酶链式反应(RT—PCR)法检测结肠癌细胞系SW480中COX-2 mRNA表达水平,用选择性COX-2抑制剂NS-398处理结肠癌细胞系SW480,Westem blot检测Stat3与PPARδ信号转导通路成员表达,噻唑蓝(MTT)比色试验检测细胞增殖状态,流式细胞技术检测细胞周期与凋亡。结果结肠癌细胞系SW480中未检测到 COX-2 mRNA表达,NS-398(75 μmol／L)作用于SW480细胞72 h后,G1期细胞比率由37．9％上升至48．6％,S期细胞比率分别由58．1％,下降至44．9％,细胞增殖受抑制。Stat3、PPARδ、Cyclin D1 与bcl-XL表达水平随NS-398作用时间延长而下降。结论选择性COX-2抑制剂NS-398可能通过非COX-2依赖途径影响结肠癌细胞的增殖。

Objective To investigate the role of selective COX-2 inhibitor NS398 on proliferation and apoptosis of colorectal cancer, and to reveal the COX-2-independent mechanism of NS-398 on colorectal cancer cell, Methods RT-PCR analysis was performed on human colon cancer cell line SW480 to detect the COX-2 mRNA expression. After addition of NS-398 （a selective COX-2 inhibitor） into culture medium, MTT assay was used to measure the absorption value 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 The expression of COX-2 mRNA was not detectable in SW480 colon cancer cells. NS-398 （75 μmol/L） inhibited the cells proliferation and induced apoptosis in colon cancer cell lines. The ratio of cells in G1 phase was increased from 37.9 % to 48.6 %, and the ratio of cells in S phase was decreased from 58.1% to 44.9%. NS398 also diminished the expression of Stat3, PPAR$, cyclin D1 and bcl-x L. Conclusion The selective COX-2 inhibitor NS-398 may inhibit the proliferation and induce apoptosis of colon cancer cell lines by blocking specific signaling pathway.