JAK/STAT3信号系统通过瘦素调控hTERT在肝癌细胞中的作用

JAK/STAT3 signaling regulates human telomerase reverse transcriptase via Leptin in hepatoma cells

目的:探讨人肝癌细胞(HepG2)中瘦素(Leptin)介导JAK/STATS信号系统对人端粒酶逆转录酶(human telomerase reverse transcriptase,hTERT)的影响,解析在肝癌细胞中Leptin诱导hTERT表达的分子机制.方法:采用Western blot测定HepG2细胞中Leptin受体的表达情况及检测Tyrphostin AG490(JAK抑制剂)处理HepG2细胞后hTERT蛋白的表达情况;应用STAT3-siRNA转染HepG2细胞,用MTT法检测细胞增殖情况、RT-PCR检测hTERT mRNA的表达、Western blot测hTERT蛋白的表达变化结果:在HepG2细胞中存在Leptin受体的表达;Western blot结果显示在AG490处理组及AG490联合Leptin处理组的蛋白表达较Leptin诱导hTERT蛋白表达量减少;而STAT3-siRNA转染HepG2细胞后,细胞增殖能力降低;在HepG2细胞中干扰STAT3片段,Leptin诱导的hTERT mRNA和蛋白的表达量减少.结论:在人肝癌细胞HepG2中存在Leptin受体表达;在肝癌HepG2细胞中,应用Leptin诱导JAK-STATS信号通路是上调hTERT表达的可能机制.

AIM：To explore the influence of Leptin mediated JAK/STAT3 signaling on human telomerase reverse transcriptase（hTERT） in human liver cancer cells（HepG2） and elucidate the molecular mechanisms by which Leptin induces hTERT expression in hepatocellular carcinoma cells.METHODS：The expression of ob-R in HepG2 cells was determined by Western blot.The expression of hTERT protein in cells after treatment with AG490 inhibitor was also detected by Western blot.Cell proliferation was detected by MTT method.The expression of hTERT mRNA was tested by RT-PCR,and the expression of hTERT protein was tested by Western blot.RESULTS：HepG2 cells expressed ob-R.Western blot analysis showed that the hTERT protein expression in AG490 treatment group and AG490 plus Leptin treatment group was lower than that of Leptin treatment group.HepG2 cell proliferation was reduced after STAT3-siRNA transfection.The expression of hTERT protein and hTERT mRNA was reduced in STAT3-siRNA transfected HepG2 cells after treatment with STAT3 inhibitor.CONCLUSION：HepG2 cells express ob-R.Leptin induced JAK-STAT3 signaling downregulates the hTERT mRNA and protein expression in hepatocellular carcinoma cells.