摘要
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,STAT3)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:Lep-tin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.
出处
《肿瘤》
CAS
CSCD
北大核心
2010年第9期735-739,共5页
Tumor