重组人生长激素体外激活人结肠癌细胞JAK2-STAT3通路

目的探讨重组人生长激素（rhGH）对不同生长激素受体（GHR）表达状态的人结肠癌细胞生长及JAK2-STAT3通路的影响。方法采用流式细胞术根据GHR表达状态不同筛选结肠癌细胞株，选择LOVO细胞株和HCT-8细胞株进入实验，采用MTT法分析rhGH对人结肠癌细胞生长的作用，采用流式细胞术进行细胞增殖指数（PI）、细胞周期分析及凋亡检测，采用蛋白质印迹法分析JAK2-STAT3通路相关分子的蛋白水平变化。结果HCT-8细胞株GHR呈阳性表达（59．6％），LOVO细胞株GHR呈阴性表达（3．5％）。rhGH显著促进HCT-8细胞生长，G2／M期比例明显高于未处理组（P=0．0073），PI升高，凋亡率降低，且pJAK2、pSTAT3、VEGF、CyelinD1、Bcl-xL蛋白表达增加。经rhGH处理后，LOVO细胞的上述各项检测指标未出现明显变化。结论rhGH促进GHR表达较高的HCT-8细胞生长，上调JAK2-STAT3信号转导通路多个关键节点的基因表达；不促进GHR低表达的LOVO细胞生长及JAK2-STAT3通路因子表达变化。

Recombinant human growth hormone activates JAK2-STAT3 pathway of human colon cells in vitro

Objective To investigate the effect of recombinant human growth hormone （rhGH） on JAK2-STAT3 signaling pathway and on the growth of human colon cancer cells at different growth hormone receptor （GHR） expression status. Methods LOVO and HCT-8 cell lines were selected after the colon cancer cells were screened using flow cytometry according to the GHR expression status. The growth of human colon cancer cells after intervention with rhGH was detected by MTT assay. The proliferation index （ PI）, cell cycle, and apoptosis were detected by flow cytometry. The expression of JAK2-STAT3 signaling pathway proteins was detected by Western blot. Results HCT-8 cell line showed positive GHR expression （59. 6% ）, and LOVO cell showed negative GHR expression （3.5%）. The growth rate of HCT-8 cells increased after rhGH treatment. Compared with the un- treated HCT-8 cells, the rhGH-treated HCT-8 cells showed reduced apoptosis, elevated PI, and increased G2/M phase cells （P = 0. 0073 ）. Western blot revealed that rhGH up-regulated the proteins of pJAK2, pSTAT3, VEGF, Cyclin D1, and Bcl-xL in HCT-8 cells. In contrast, no such changes were observed in LOVO cells treated with rbGH. Conclusions rhGH may promote the growth of HCT-8, the cell line of high GHR expression, and up-regulate the expression of a number of key nodes in JAK2-STAT3 signaling pathway. However, rhGH may not affect LOVO, the cell line of low GHR expression.