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目的:通过分析抑瘤素M(oncostatin M,OSM)对肝癌细胞生长的效应,研究其影响细胞增殖的分子机制。方法:OSM处理SMMC-7721和Hep G2肝癌细胞系,观察细胞的增殖速率和形态变化,结合特异性β-半乳糖苷酶染色和细胞周期分析,研究OSM是否通过诱导肝癌细胞进入衰老状态来抑制其增殖;进一步通过监测细胞周期抑制蛋白p16、p21、p27和癌基因c-Myc的表达变化,分析OSM诱导细胞衰老的原因。结果:OSM可以抑制肝癌细胞系生长,且抑制率呈现一定剂量依赖性;细胞形态变化和β-半乳糖苷酶染色进一步证实OSM可诱导细胞衰老。细胞周期分析表明OSM阻滞肝癌细胞于G0/G1期,并伴随p21和p27周期抑制蛋白的表达增高。最后,通过分析STAT3信号途径下游癌基因c-Myc的转录与蛋白水平,表明OSM可能是通过癌基因的激活而诱导细胞的衰老。结论:由癌基因激活而导致的细胞衰老,是机体的一种防御机制。OSM通过激活STAT3信号途径、上调癌基因cMyc表达的同时,也加速了细胞的衰老,从而最终表现为对肝癌细胞增殖的抑制作用。
OBJECTIVE: To investigate the molecular mechanism of oncostatin M (OSM) on the growth of hepatocellular carcinoma cells and to study its molecular mechanism of affecting cell proliferation. Methods: OSM treatment of SMMC-7721 and Hep G2 hepatocellular carcinoma cell lines, observe the proliferation rate and morphological changes of cells, combined with specific β-galactosidase staining and cell cycle analysis to study whether OSM through the induction of liver cancer cells into the aging state to suppress The proliferation and proliferation of OSM were further analyzed. The reasons of cell senescence induced by OSM were further analyzed by monitoring the changes of cell cycle arrest proteins p16, p21, p27 and oncogene c-Myc. Results: OSM could inhibit the growth of hepatocellular carcinoma cells in a dose-dependent manner. Morphological changes and β-galactosidase staining further confirmed that OSM can induce cell senescence. Cell cycle analysis showed that OSM blocks hepatoma cells in the G0 / G1 phase, accompanied by increased expression of p21 and p27 cycle arrestin. Finally, by analyzing the transcription and protein level of downstream oncogene c-Myc in STAT3 signaling pathway, OSM may induce cell senescence through the activation of oncogene. CONCLUSIONS: Cell senescence caused by oncogene activation is a defense mechanism of the body. OSM activates STAT3 signaling pathway and up-regulates oncogene cMyc expression, accelerates cell senescence, and eventually manifests itself as an inhibitory effect on the proliferation of hepatocellular carcinoma cells.