白藜芦醇抑制IGF-I促人肺腺癌A549细胞增殖作用及其机制的研究

目的观察白藜芦醇对IGF-I介导人肺腺癌细胞增殖的影响及其IGF-I受体、AKT、p-AKT、ERK1/2、p-ERK1/2的表达变化。方法应用MTT方法测定细胞增殖,采用RT-PCR检测IGF-I受体mRNA表达,并应用免疫印迹方法检测AKT、p-AKT及ERK1/2、p-ERK1/2蛋白表达水平。结果不同浓度IGF-I(2.5～15nM)可显著促进A549细胞增殖(F=22.321,P=0.011),白藜芦醇(6.25～50μM)与10nMIGF-I共作用于A549细胞,均可抑制IGF-I的促A549细胞增殖作用(F=11.211,P=0.032),其中尤以25μM、50μM白藜芦醇的抑制增殖作用显著(P=0.034;P=0.012),并且,白藜芦醇可有效降低IGF-I受体mRNA表达以及降低IGF-I增强的AKT及ERK1/2磷酸化。结论白藜芦醇能够抑制IGF-I介导的A549肺癌细胞增殖,其作用机制可能与白藜芦醇降低A549肺癌细胞IGF-I受体mRNA表达及AKT、ERK1/2磷酸化相关。

Study on the the Inhibitory Effect of Resveratrol on IGF-I Enhancing A549 Lung adenocarcinoma Cells Proliferation and its mechanisms

OBJECTIVE To observe the effects of resveratrol on the proliferation of the lung adenocarcinoma cell line A549 cells induced by IGF-I and the expression of IGF-IR,AKT,p-AKT,ERK1/2 and p-ERK1/2.METHODS Methyl thiazolyl tetrazolium(MTT)assay was used to quantify the cell proliferation rate.The expression of IGF-IR mRNA was measured by RT-PCR.Western blot was employed to detect the expression of AKT,p-AKT,ERK1/2 and p-ERK1/2 protein.RESULTS Different doses(2.5nM-15nM)of IGF-I increased the A549 cells proliferation(F = 22.321,P = 0.011).After resveratrol with IGF-I treated,resveratrol may inhibit the proliferation of A549 cells induced by IGF-I(F = 11.211,P = 0.032),especially in a dose of 25.0 and 50μM(P = 0.034;P = 0.012).Resveratrol could downregulate IGF-IR mRNA expression and phosphorylation of Akt and ERK1/2 protein enhanced by IGF.CONCLUSION Resveratrol has an inhibitory effect on the proliferation of the lung adenocarcinoma cell line A549 cells induced by IGF-I via the decrease of IGF-I receptor expression and blocking the IGF-I mediated activation of Akt and ERK1/2 pathway.