IGF2BP3通过激活PI3K/AKT/mTOR通路促进肝癌细胞增殖

IGF2BP3 promotes the proliferation of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR pathway

目的探讨IGF2BP3(胰岛素样生长因子2-mRNA结合蛋白3)过表达对肝癌细胞增殖的影响及其可能的分子机制,为临床治疗肝癌提供实验基础及理论依据。方法qRT-PCR和Western Blot检测肝癌细胞系HuH-7、MHCC97H中转染IGF2BP3过表达质粒后IGF2BP3的mRNA和IGF2BP3、AKT、p-AKT、S6、p-S6蛋白表达水平;CCK-8、EdU实验检测细胞的增殖能力;皮下成瘤实验检测IGF2BP3对肿瘤生长作用,免疫组织化学法检测IGF2BP3、Ki67在过表达IGF2BP3组和对照组的表达。结果在肝癌细胞中转染IGF2BP3过表达质粒后,IGF2BP3的mRNA和蛋白表达水平显著升高且有统计学意义(P<0.001),过表达IGF2BP3促进肝癌细胞增殖(P<0.01);过表达IGF2BP3促进肝癌体内生长,免疫组化显示IGF2BP3、Ki67表达上调;Western Blot结果显示p-AKT、p-S6表达上调;抑制AKT活性后,肝癌细胞增殖能力明显减弱(P<0.01)。结论过表达IGF2BP3可能通过激活PI3K/AKT/mTOR信号通路促进肝癌增殖。

Objective To investigate the effect of IGF2BP3(insulin-like growth factor 2-mRNA binding protein 3)overexpression on hepatoma cell proliferation and its possible molecular mechanism,and to provide experimental basis and theoretical basis for clinical treatment of hepatoma.Methods mRNA and protein expression levels of IGF2BP3,AKT,p-AKT,S6 and p-S6 were detected in HuH-7 and MHCC97H HCC cells transfected with IGF2BP3 overexpression plasmid.CCK-8 and EdU assay were used to detect cell proliferation.The effect of IGF2BP3 on tumor growth was detected by subcutaneous tumorigenization test,and the expressions of IGF2BP3 and Ki67 in overexpressed IGF2BP3 group and control group were detected by IHC.Results After transfection of IGF2BP3 overexpression plasmid,the mRNA and protein expression levels of IGF2BP3 were significantly increased with statistical significance(P<0.001),and overexpression of IGF2BP3 promoted the proliferation of liver cancer cells(P<0.01).Overexpression of IGF2BP3 promoted the growth of liver cancer,and immunohistochemistry showed that the expressions of IGF2BP3 and Ki67 were up-regulated.Western Blot showed that the expressions of p-AKT and p-S6 were up-regulated.The proliferation ability of hepatocellular carcinoma cells was significantly decreased after AKT inhibition(P<0.01).Conclusion Overexpression of IGF2BP3 may promote the proliferation of liver cancer by activating PI3K/AKT/mTOR signaling pathway.