瘦素激活MAPK和PI3K信号通路上调Bcl-2调控肺癌A549细胞增殖

Leptin mediates proliferation of lung cancer A549 cells by upregulation of Bci-2 through activation of MAPK and PI3K signaling pathway

目的探讨瘦素促进肺腺癌A549细胞增殖的分子机制。方法瘦素处理A549细胞，Westernblotting方法检测细胞内Bcl-2的表达；MAPK及P13K信号通路阻滞剂处理A549细胞，Westernblotting方法检测信号通路下游复合物ERK1／2、P—ERK1／2、Akt、P—Akt等蛋白及细胞内Bcl-2的表达变化。结果瘦素促进细胞内Bcl-2的表达，且具有浓度依赖性。瘦素可促进ERK1／2、Akt的磷酸化；用MAPK及P13K信号通路阻滞剂预处理细胞，可以阻滞ERK1／2、Akt的磷酸化，并能够抑制Bcl-2蛋白的表达。结论瘦素可能通过MAPK和P13K通路，介导抗凋亡蛋白Bcl-2的过度表达而使肺腺癌A549细胞呈持续增殖，从而为开发抗肿瘤药物提供新思路。

Objective To investigate the possible molecular mechanism of leptin in stimulating the proliferation of lung adenocarcinoma A549 cells. Methods A549 cells were treated with different concentrations of leptin, and the expression of Bel-2 was evaluated by Western blotting. The expressions of ERK1/2, p-ERK1/2, Akt, p-Akt,and Bcl 2 were detected by Western blotting after MAPK and PI3K signaling pathway blockers were used. Results Leptin increased the expression of Bcl-2 in a dosedependent manner. Leptin also caused ERK1/2 and Akt phosphorylation. Pretreatment with inhibitors of MAPK and PI3K inhibited these responses, and abolished Bcl-2 expression. Conclusions Leptin may mediate the overxpression of anti-apoptotic gene Bcl-2 by activating MAPK and PI3K pathway to promote the continues proliferation of A549 cells, and may represent a target for anticancer drug development.