中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2010年
12期
903-906
,共4页
郭人花%王同杉%陈晓锋%黄祖瑚%束永前
郭人花%王同杉%陳曉鋒%黃祖瑚%束永前
곽인화%왕동삼%진효봉%황조호%속영전
肝肿瘤%信号传导%细胞增殖%凋亡%他莫昔芬%雷帕霉素
肝腫瘤%信號傳導%細胞增殖%凋亡%他莫昔芬%雷帕黴素
간종류%신호전도%세포증식%조망%타막석분%뢰파매소
Liver neoplasms%Signal transduction%Cell proliferation%Apoptosis%Tamoxifen%Rapamycin
目的 探讨mTOR信号分子和凋亡抑制因子survivin在他莫昔芬处理的肝癌HepG2细胞中的表达变化.方法 采用逆转录聚合酶链反应(RT-PCR)、Western blot和双荧光素酶报告基因检测方法,检测HepG2细胞在他莫昔芬处理前后survivin的表达和p70S6K的活性;流式细胞仪检测细胞凋亡.结果 20μmol/L的他莫昔芬在诱导HepG2细胞凋亡的同时,可使survivin在HepG2细胞中的表达减少,同时下调了 p70S6K的活性.mTOR的特异性抑制剂雷帕霉素和他莫昔芬联合处理HepG2细胞后,HepG2细胞增殖率较对照组下降了 64.7%,差异有统计学意义(P＜0.05),同时survivin蛋白表达明显下降,而survivin mRNA表达无明显变化.结论 他莫昔芬和雷帕霉素能够协同下调HepG2细胞中survivin的表达,他莫昔芬下调HepG2细胞中survivin的表达可能是通过PI3K/Akt/mTOR信号通路调节其转录和转录后水平,进而诱导肝癌细胞凋亡.
目的 探討mTOR信號分子和凋亡抑製因子survivin在他莫昔芬處理的肝癌HepG2細胞中的錶達變化.方法 採用逆轉錄聚閤酶鏈反應(RT-PCR)、Western blot和雙熒光素酶報告基因檢測方法,檢測HepG2細胞在他莫昔芬處理前後survivin的錶達和p70S6K的活性;流式細胞儀檢測細胞凋亡.結果 20μmol/L的他莫昔芬在誘導HepG2細胞凋亡的同時,可使survivin在HepG2細胞中的錶達減少,同時下調瞭 p70S6K的活性.mTOR的特異性抑製劑雷帕黴素和他莫昔芬聯閤處理HepG2細胞後,HepG2細胞增殖率較對照組下降瞭 64.7%,差異有統計學意義(P＜0.05),同時survivin蛋白錶達明顯下降,而survivin mRNA錶達無明顯變化.結論 他莫昔芬和雷帕黴素能夠協同下調HepG2細胞中survivin的錶達,他莫昔芬下調HepG2細胞中survivin的錶達可能是通過PI3K/Akt/mTOR信號通路調節其轉錄和轉錄後水平,進而誘導肝癌細胞凋亡.
목적 탐토mTOR신호분자화조망억제인자survivin재타막석분처리적간암HepG2세포중적표체변화.방법 채용역전록취합매련반응(RT-PCR)、Western blot화쌍형광소매보고기인검측방법,검측HepG2세포재타막석분처리전후survivin적표체화p70S6K적활성;류식세포의검측세포조망.결과 20μmol/L적타막석분재유도HepG2세포조망적동시,가사survivin재HepG2세포중적표체감소,동시하조료 p70S6K적활성.mTOR적특이성억제제뢰파매소화타막석분연합처리HepG2세포후,HepG2세포증식솔교대조조하강료 64.7%,차이유통계학의의(P＜0.05),동시survivin단백표체명현하강,이survivin mRNA표체무명현변화.결론 타막석분화뢰파매소능구협동하조HepG2세포중survivin적표체,타막석분하조HepG2세포중survivin적표체가능시통과PI3K/Akt/mTOR신호통로조절기전록화전록후수평,진이유도간암세포조망.
Objective The aim of this study was to investigate the changes in mTOR activity and survivin expression in liver cancer cell line HepG2 cells treated with tamoxifen. Methods Survivin transcription level and p70S6K was demonstrated by PCR, dual-luciferase reporter assay and Western blot analysis, respectively, and the apoptosis in the HepG2 cells was detected by flow cytometry. Results Tamoxifen leads to apoptosis of the cells and reduction in survivin expression, as well as a dramatic reduction in the activated form of p70S6K. Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduced the snrvivin protein level but not affected the survivin transcription, indicating that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells.Conclusions Our results suggest that tamoxifen down-regulates survivin expression in HepG2 cells and it is mediated by transcriptional and post-transcriptional level via PI3K/Akt/mTOR pathway to induce apoptosis.
