罗格列酮抑制卵巢癌生长的体内外实验研究  

Study on the Inhibitory Effects of Rosiglitazone on the Growth of Ovarian Cancer Cells in Vitro and in Vivo

作　　者：孙文洲[1] 于丽波[1] 周学军[1] 冯雪[2] 潘萌[2] 李文乐[1] 刘洋[1] 

机构地区：[1]哈尔滨医科大学附属第三医院,黑龙江哈尔滨150081 [2]哈尔滨医科大学公共卫生学院,黑龙江哈尔滨150081

出　　处：《实用妇产科杂志》2012年第1期36-39,共4页Journal of Practical Obstetrics and Gynecology

基　　金：哈尔滨市科技创新人才研究专项基金项目(编号:2008RFQXS095)

摘　　要：目的:探讨罗格列酮(RGZ)对人卵巢浆液性乳头状囊腺癌SKOV3细胞生长的抑制作用。方法:应用噻唑蓝法(MTT)检测RGZ对卵巢癌细胞增殖的影响;应用4',6-二脒基-2-苯基吲哚(DAPI)荧光染色观察细胞凋亡形态学变化;反转录-聚合酶链反应(RT-PCR)检测RGZ对SKOV3细胞PPARγ、Bcl-2及Caspase-3 mRNA表达的影响;建立卵巢癌裸鼠移植瘤模型,分为RGZ治疗组及对照组,观察RGZ对移植瘤体积和重量变化的影响。结果:①MTT法检测不同浓度RGZ组(1、10、50、100、200μmol/L)细胞生长抑制率与对照组比较,差异均有统计学意义(P<0.05),并呈浓度依赖性抑制;②DAPI荧光染色发现,RGZ作用24小时后,细胞核浓缩,着色较深呈亮蓝色,部分细胞核破裂呈碎片状或多边形;③RT-PCR检测发现,不同浓度RGZ(10、50、100μmol/L)作用于SKOV3细胞24小时后PPARγ、Caspase-3 mRNA表达水平上调,而Bcl-2 mRNA表达水平下降,与对照组比较,差异有统计学意义(P<0.05);④细胞接种26天后,RGZ各用药组(4、12、60、120mg/kg)裸鼠移植瘤体积增长缓慢,其抑瘤率与对照组比较,差异有统计学意义(P<0.05)。结论:RGZ可明显抑制SKOV3细胞的生长,诱导其凋亡,并呈浓度依耐性,通过激活PPARγ-Bcl-2-Caspase-3细胞凋亡信号通路而实现抑制肿瘤细胞生长的作用。Objective：To explore the inhibitory effect of Rosiglitazone（RGZ） on the growth of human ovarian cancer SKOV3 cells in vitro and in vivo.Methods：The proliferation of SKOV3 cells were evaluated by MTT assay after treatment with RGZ.The apoptosis was determined by DAPI fluorescence,the expressions of PPARγ、Caspase-3 and Bcl-2 mRNA in SKOV3 cells were evaluated by RT-PCR.After the subcutancous transplantation of SKOV3 cells in the back of nude mice,the mice were randomly divided into control group and therapeutic group.The body weight of nude mice and the growth of tumor were measured.Results：RGZ inhibited the proliferation of SKOV3 cells and induced apoptosis in a dose-dependent manner.The expressions of PPARγ and Caspase-3 mRNA in SKOV3 cells were significantly increased and the expression of Bcl-2 mRNA was markedly decreased 24 hours after the treatment of RGZ at different concentrations（10、50、100 μmol/L）,the differences were significant compared with those data in control group（P〈0.05）.The growth of transplanted tumor was slower in therapeutic group 26 days after treament at different dosages（4、12、60、120 mg/kg）compared with that in control group（P〈0.05）.Conclusions：RGZ can inhibit the growth of SKOV3 cells and induces the apoptosis in a dose-dependant manner.This result may be obtained by activating PPARγ-Bcl-2-Caspase-3 apoptotie signaling pathway.

关 键 词：罗格列酮 卵巢癌 裸鼠移植瘤 

分 类 号：R737.31[医药卫生—肿瘤]