白藜芦醇抑制EGF诱导人肺腺癌A549细胞侵袭  

Resveratrol Inhibits EGF-induced Invasion of Human Lung Adenocarcinoma A549 Cells

作　　者：黄宁宇[1] 芦宏[1] 常丽君[1] 张红伟[1] 张灏[2] 李冠武[1] 

机构地区：[1]汕头大学医学院肿瘤分子生物学开放实验室,汕头515041 [2]汕头大学医学院肿瘤研究中心/肿瘤医院中西医结合科,汕头515041

出　　处：《中国肺癌杂志》2010年第4期287-291,共5页Chinese Journal of Lung Cancer

摘　　要：背景与目的侵袭转移是人肺腺癌死亡的主要原因,表皮生长因子(epidermal growth factor,EGF)可通过活化ERK和PI3K-Akt信号通路,促进人肺腺癌A549细胞侵袭。本实验旨在研究白藜芦醇抑制EGF诱导体外A549细胞侵袭的作用,并初步探讨其机制。方法采用MTT法确定白藜芦醇对A549细胞无明显毒性的浓度范围,并以该浓度范围内的白藜芦醇作用EGF诱导的A549细胞,Transwell小室法检测其抑制细胞侵袭作用,明胶酶谱法分析细胞的MMP-2活性变化,Westernblot检测EGF信号通路相关蛋白表达。结果30μM内的白藜芦醇无明显的细胞毒性,20μM处理的受EGF诱导的A549细胞侵袭能力明显降低,MMP-2分泌减少,胞内p-ERK1/2和PI3K(0.5h-6h)含量下降。结论20μM白藜芦醇可有效抑制A549细胞侵袭,其机制可能是通过抑制ERK通路和PI3K-Akt通路中相关蛋白激活,最终降低MMP-2的分泌。Background and objective Invasion and metastasis are the primary causes of death in patients with pulmonary carcinoma.The epidermal growth factor （EGF） stimulates A549 cells invasion greatly through activating ERK and PI3K-Akt signaling pathway.The aim of this study is to elucidate the inhibitory effect of Resveratrol on EGF-induced invasive ability of A549 cells in vitro and explore the molecular mechanism.Methods The cytotoxicity of Resveratrol was evaluated by methyl thiazolyltetrazolium （MTT） assay.Then,the A549 cells were treated with EGF and non-cytotoxic concentration of Resveratrol.The cells’ invasion were detected by Boyden chamber assay;MMP-2 activity was determined by gelatine zymography assay;the changes of the related proteins were detected by Western blot.Results Resveratrol was not toxic to A549 cells at the concentration between 0 to 30 μM.The invasion ability of EGF-induced A549 cells was decreased after treatment with 20 μM resveratrol for 24 h,accompanied by the inhibition of MMP-2 secretion.And the levels of p-ERK1/2,PI3K （within 6 h） were suppressed too.Conclusion 20 μM Resveratrol inhibits A549 cells’ invasion possibly through the suppression of the activation of ERK and PI3K-Akt signaling pathways,subsequently exerting inhibitory effect on MMP-2.

关 键 词：白藜芦醇 ERK1/2(细胞外信号调节激酶1/2) PI3K(磷脂酰肌醇三羟基激酶) 

分 类 号：R734.2[医药卫生—肿瘤]