瘦素激活ERK1/2信号通路诱导肺癌细胞增殖

Leptin Activates ERK1/2 Signaling Pathway and Induces Lung Cancer Cell Proliferation

背景与目的:研究瘦素(leptin)及其瘦素受体(OB-Rb)在肺癌和癌旁组织中的表达情况,并探讨瘦素介导的ERK1/2通路在促进人肺癌A549细胞增殖过程中的作用。材料与方法:采用免疫组织化学法检测24例人肺癌和癌旁组织中瘦素及其OB-Rb的表达情况,同时采用免疫荧光染色和RT-PCR法检测A549中OB-Rb的表达,并用四甲基偶氮唑盐比色(MTT)法和免疫印迹(Westernblot)法检测瘦素对A549细胞促增殖效应以及ERK1/2是否介导了该作用。结果:人肺癌组织中瘦素及其OB-Bb阳性表达率(分别为83.37%,66.7%)明显高于癌旁肺组织(分别为33.3%,29.2%)(P<0.01);A549细胞中存在OB-Rb的表达,且瘦素能明显促进A549细胞增殖,经100ng/ml瘦素处理24h后,其增殖效应最显著,并且100ng/ml瘦素处理20min后,ERK1/2的磷酸化显著增加。应用特异性的ERK激酶抑制剂PD98059抑制ERK1/2的激活后,瘦素的促A549增殖作用明显减弱。结论:瘦素及其受体在肺癌组织中高表达并通过激活ERK1/2信号通路促进A549细胞的增殖,表明瘦素可能通过刺激ERK1/2信号通路的持续激活而促进肺癌的发生发展。

BACKGROUND AND AIM： This study was to evaluate leptin and OB-Rb expression in human lung cancer and adjacent normal lung tissuee, and xplore the role of extracellular singnal-regulated kinase 1/ 2（ERK1/ 2） in teptin-induced lung cancer A549 cell proliferation . MATERIALS AND METHODS： Immunohistochemical staining was used to evaluate the protein expression of leptin and OB-Rb in tumor tissues and samples of corresponding adjacent lung tissue, the expression of OB-Rb in A549 cells was evaluated by fluoroimmunoassay and reverse transcription polymerase chain reaction（RT-PCR） The action of leptin on A549 was examined by MTT assay to determine cell proliferation, and activation of extracellular singnal-regulated kinase 1/2（ERK1/2） was assessed by Western blot. RESULTS： The positive protein expression of leptin and OB-Rb were detected in a significantly greater proportion of lung cancer（83.37% and 66.7%, respectively）than adjacent normal lung tissue（33.3% and 29.2%, respectively）, P 〈 0.01. Fluoroimmunoassay and RT-PCR showed the presence of OB-Rb in A549 cells. Leptin could stimulate the proliferation of A549 cells, and this effect was maximal at 100 ng/ml after 24-hour treatment. Blocking ERK1/ 2 phosphorylation by PD98059 significantly reduced the proliferation of A549 ceils stimulated by leptin. CONCLUSION： Enhanced expression of leptin and OB-Rb in lung cancer and leptin could promote the proliferation of A549 cells by activating ERK1/2 signaling pathway suggested that continued activation of ERK1/2 pathways by leptin might promote lung cancer growth and development.