目的: 研究瘦素(leptin)对人脑胶质瘤生长的影响, 并探讨其分子机制。方法: 以不同浓度leptin刺激人脑胶质瘤细胞U87-MG后, MTT法检测其细胞增殖的变化, FCM法检测leptin对U87-MG细胞周期及凋亡的影响; Real-time PCR法及Western印迹法检测leptin作用后, U87-MG细胞中信号转导和转录激活因子3(signal transducers and activators of transcription 3, STAT 3)的表达; 建立裸鼠皮下成瘤模型, 进一步检测leptin对人脑胶质瘤裸鼠移植瘤生长及STAT3表达的影响。结果: Leptin可以显著促进人脑胶质瘤细胞U87-MG的体外生长, 并呈剂量依赖性和时间依赖性; leptin促进U87-MG细胞由G₀/G₁期向S期转变, 但对细胞凋亡无任何影响; U87-MG细胞中STAT3 mRNA和蛋白表达水平被显著提高。裸鼠皮下成瘤实验提示, leptin可以显著促进U87-MG细胞移植瘤生长, 并提高移植瘤组织中STAT3的表达水平。结论: Leptin可以显著促进人脑胶质瘤生长, 其作用机制可能与JAK2-STAT3信号转导通路的活化有关。

Objective: To investigate the effect of leptin on the growth of human glioma, and to elucidate its molecular mechanism.Methods: U87-MG human glioma cells were treated with different concentrations of leptin, and the cell proliferation was detected by MTT assay. The effects of leptin on cell cycle and apoptosis of U87-MG were analyzed by flow cytometry. Real-time PCR and Western blot were used to detect the expressions of signal transducers and activators of transcription 3(STAT3) in U87-MG cells. The subcutaneous tumor model in nude mice was used to further detect the effects of leptin on the growth of human glioma xenografts and expression of STAT3 in vivo.Results: Leptin significantly increased the growth of U87-MG human glioma cells in a dose-dependent and time-dependent manner. Flow cytometry revealed that leptin stimulated transformation of U87-MG cells from G₀/G₁ phase to S phase, but had no effects on the cell apoptosis. STAT3 mRNA and protein expressions in U87-MG cells were significantly upregulated. The subcutaneous tumor model in nude mice showed that leptin significantly increased the growth of U87-MG xenografts and elevated STAT3 expression.Conclusion: Leptin can significantly increase the growth of human glioma, and its mechanism might be related to the activation of the JAK2-STAT3 signaling pathway.