癌变·畸变·突变 ›› 2009, Vol. 21 ›› Issue (1): 30-035.doi: 10.3969/j.issn.1004-616x.2009.01.008

• 论著 • 上一篇    下一篇

瘦素激活ERK1/2信号通路诱导肺癌细胞增殖

张妍蓓,华天凤,何凤莲,方 明,胡碧丹,徐 轲,刘荣玉   

  1. 安徽医科大学第一附属医院老年呼吸内科,合肥 230022
  • 收稿日期:2008-08-27 修回日期:2008-11-06 出版日期:2009-01-30 发布日期:2009-01-30

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

ZHANG Yan-bei,HUA Tian-feng,HE Feng-lian,FANG Ming,HU Bi-dan, XU Ke, LIU Rong-yu   

  1. Department of Geriatric Pulmonology, The First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui,China
  • Received:2008-08-27 Revised:2008-11-06 Online:2009-01-30 Published:2009-01-30

摘要: 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(Western blot)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100 ng/ml瘦素处理24 h后,其增殖效应最显著,并且100 ng/ml瘦素处理20 min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。

关键词: 肺癌, 瘦素, 受体, ERK1/2, A549细胞, 增殖

Abstract: 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 leptin-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 cells 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.

Key words: lung cancer, leptin, receptor, ERK1/2, A549, proliferation