p62对结肠癌细胞生长的影响

Effect of p62on colorectal cancer growth

目的探讨p62在结肠癌发展中的作用及其机制。方法 p62短发夹RNA(shRNA)慢病毒感染结肠癌细胞SW480,构建稳定表达细胞株。CCK-8检测p62对细胞增殖和化疗敏感性的影响,裸鼠荷瘤检测p62对体内肿瘤生长的影响,活性氧(ROS)水平检测p62对细胞内氧化应激状态的作用。结果下调p62表达可以抑制SW480细胞体外增殖和体内生长(P<0.05),提高对奥沙利铂的敏感性。同时,p62抑制后结肠癌细胞内的ROS水平升高(P<0.01),LC3Ⅱ表达下调,LC3Ⅱ/LC3Ⅰ比值下降(P<0.05)。结论 p62是结肠癌生长和进展中的重要因素,可能通过调控ROS产生和自噬等多种机制促进结肠癌发展。

Objective To investigate the effect and underlying mechanisms of p62 in the progression of colorectal cancer cells.Methods Colorectal cancer cell line SW480 was infected by p62 shRNA lentivirus and the stable cells with knockdown of p62 were established.The effects of p62 on cell proliferation and chemosensitivity were examined by CCK-8assay.In vivo xenograft study was performed.Then the ROS and autophagic status were determined.Results Downregulation of p62 significantly inhibited the SW480 cell proliferation in vitro and tumor growth of the xenografts（P〈0.05）.The chemosensitivity of SW480 to oxaliplatin was markedly enhanced.Meanwhile,the cells with low p62 level had elevated ROS production（P〈0.01）,decreased LC3 Ⅱ expression and LC3Ⅱ/LC3Ⅰ ratio（P〈0.05）when p62 was knockdown.Conclusion p62 is a critical component in the progression of colorectal cancer,which could promote cancer growth by maintaining ROS balance and autophagy.