他莫昔芬对人肝胚细胞瘤HepG2细胞中mTOR和survivin表达的影响研究

摘要

Objective To study the effects of tamoxifen on the expressions of mTOR and Survivin in human hepatob-lastoma HepG2 cells. Methods This experiment used PCR, dual-luciferase report gene assay system and the Western blot biological method to investigate the transcription levels and protein expression levels of survivin and p70S6k in HepG2 cells treated with tamoxifen. Results Tamoxifen significantly inhibited the protein expression of survivin, and reduced the syn-thesis of p70S6k kinase. 20μM tamoxifen could effectively inhibit the transcription level of survivin mRNA. It was found that the protein expression level of survivin was decreased significantly in the HepG2 cells which were treated with mTOR specific inhibitor rapamycin, but the transcription of survivin gene was not affected. The results indicated that tamoxifen and rapamycin synergistically inhibited the expression of Survivin in HepG2 cells. Conclusion Tamoxifen effectively inhibited the expression of survivin factor in HepG2 cells by regulating PI3K/Akt/mTOR signal pathway.%目的：研究他莫昔芬对人肝胚细胞瘤HepG2细胞中mTOR和survivin表达的影响。方法运用RT-PCR、双荧光素酶报告基因检测系统和Western blot生物学方法对接受他莫昔芬刺激的HepG2细胞内survivin和p70S6k的转录水平和蛋白表达水平进行分析。结果他莫昔芬明显抑制了survivin的蛋白表达，并且减少了p70S6k激酶的合成。20μM的他莫昔芬即可有效抑制survivin mRNA的转录。运用mTOR特异性抑制因子雷帕霉素处理HepG2细胞，发现HepG2细胞内survivin的蛋白表达水平明显下降，但是雷帕霉素并未影响survivin基因的转录，表明他莫昔芬和雷帕霉素通过协同作用抑制HepG2细胞内survivin的表达。结论他莫昔芬通过调节PI3K/Akt/mTOR 信号通路有效地抑制了HepG2细胞内survivin 因子的表达。