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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

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【作者】 华天凤何凤莲方明胡碧丹赵卉张志红张妍蓓

【Author】 HUA Tian-feng,HE Feng-lian,FANG Ming,HU Bi-dan,ZHAO Hui,ZHANG Zhi-hong,ZHANG Yan-bei(Department of Geriatric Respiratory Medicine,First Affiliated Hospital of Anhui Medical University,Hefei 230022,China)

【机构】 安徽医科大学第一附属医院老年呼吸内科

【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。

【Abstract】 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.

【基金】 安徽省自然科学基金资助项目(编号:070413068)
  • 【分类号】R734.2
  • 【被引频次】1
  • 【下载频次】222
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