瘦素通过激活STAT3信号通路促进人肺腺癌细胞增殖  

Leptin promotes cell proliferation of human lung adenocarcinoma by activating STAT3 signaling pathway

作　　者：华天凤[1] 何凤莲[1] 方明[1] 胡碧丹[1] 赵卉[1] 张志红[1] 张妍蓓[1] 

机构地区：[1]安徽医科大学第一附属医院老年呼吸内科,合肥230022

出　　处：《肿瘤》2009年第5期459-463,共5页Tumor

基　　金：安徽省自然科学基金资助项目(编号:070413068)

摘　　要：目的:探讨瘦素(leptin)及其受体OB-Rb在人肺腺癌组织中的表达,并选用人肺腺癌A549细胞株探讨瘦素是否通过激活JAK2-STAT3信号通路发挥其促细胞增殖作用。方法:免疫组织化学法检测人肺腺癌及癌旁组织中瘦素及OB-Rb蛋白的表达情况,Western印迹法检测A549细胞中OB-Rb表达情况;MTT法检测A549细胞中瘦素对细胞增殖作用的影响,Western印迹法检测STAT3蛋白的活化程度。结果:人肺腺癌组织中瘦素及OB-Bb的阳性表达率分别为68.6%和48.6%,明显高于癌旁组织(P<0.05)。人肺腺癌A549细胞中存在OB-Rb的表达,瘦素能明显促进A549细胞的增殖;在0～100ng/mL范围内瘦素浓度越高,细胞的增殖效应越显著,并且经100ng/mL瘦素处理后,STAT3的活化程度明显增高;而JAK酶抑制剂AG490能明显抑制瘦素对A549细胞的增殖作用。结论:瘦素和OB-Rb在肺腺癌组织中表达上调,表明其可能参与了肺腺癌的发生发展。瘦素可能通过激活JAK2-STAT3信号转导途径促进肺腺癌细胞的增殖。Objective：To study the expressions of leptin and its receptor（OB-Rb）in human lung cancer tissues and determine whether it promoted cell proliferation of human lung adenocarcinoma by activating JAK2 and activator of transcription3 （STAT3） signaling pathway. Methods： Immunohistochemical staining method was used to detect the protein expressions of leptin and OB-Rb in lung adenocarcinoma tissues and corresponding adjacent lung tissues. Western blotting was used to detect the expression of OB-Rb in A549 cells. MTT assay was used to determine the effect of leptin on the cell proliferation. And Western blotting was used to explore the activation degree of STAT3. Results： The expressions of leptin and OB-Rb （68.6% and 48.6%） were significantly higher in human lung adenocarcinoma tissues than that in the adjacent normal lung tissues （25.7% and 22.9%）. Western blotting showed the expression of OB-Rb in A549 cells. Leptin at 0 to 100 ng/mL markedly stimulated the proliferation of A549 cells in a concentration-dependent manner. The activation degree of STAT3 was significantly increased after treatment with leptin 100 ng/mL for 24 h. AG490, JAK inhibitor, significantly reduced the proliferation of A549 cells stimulated by leptin. Conclusion： The expressions of leptin and OB-Rb were up-regulate in human lung adenocarcinoma tissues indicating that they participated in the carcinogenesis and development of lung adenocarcinoma. Leptin may promote the proliferation of A549 cells by activating JAK2-STAT3 signaling pathway.

关 键 词：腺瘤病 肺 瘦素 信号转导 STAT转录因子类 细胞增殖 

分 类 号：R734.2[医药卫生—肿瘤] R730.23[医药卫生—临床医学]