罗格列酮促进卵巢癌细胞凋亡的体内实验研究  

Study on the Promotion Effects of Rosiglitazone on the Apoptosis of Ovarian Cancer Cells in Vivo

作　　者：包文影 于丽波[1] 孙文洲[1] 毕玉美[1] 杨桂春[1] 李明慧[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

出　　处：《中国肿瘤》2014年第8期699-703,共5页China Cancer

基　　金：哈尔滨市科技创新人才研究专项基金项目(2008RFQXS095)

摘　　要：[目的]探讨过氧化物酶体增殖物激活受体γ(PPAR-γ)配体罗格列酮(RGZ)对人卵巢浆液性乳头状囊腺癌SKOV3细胞的抑制作用。[方法]建立卵巢癌SKOV3细胞裸鼠移植瘤模型,观察不同剂量RGZ对移植瘤体积的影响;HE染色观察各组移植瘤组织细胞形态学变化;免疫细胞化学法观察移植瘤中Bcl-2、Cytochrome C蛋白表达水平。[结果]RGZ组(4mg/kg,12mg/kg,60mg/kg,120mg/kg)裸鼠移植瘤体积分别为0.190±0.023mm3、0.065±0.003mm3、0.195±0.004mm3和0.182±0.023mm3,较对照组(0.300±0.016mm3)均明显缩小,差异有统计学意义(P<0.05)。抑瘤率分别为36.7%、78.3%、35.0%和40.0%。HE染色观察RGZ作用SKOV3细胞后有变性细胞、单细胞死亡及大面积的凝固性坏死。Bcl-2在RGZ组(60mg/kg,120mg/kg)中的表达较对照组显著下调,Cytochrome C在RGZ组(60mg/kg,120mg/kg)中的表达较对照组显著上调,差异均有统计学意义(P<0.05)。[结论]RGZ对卵巢癌裸鼠移植瘤有明显抑制作用,可促进凋亡。提示PPAR-γ可能成为卵巢癌治疗的新分子靶点。[ Purpose ] To investigate the anti-tumor effect of peroxisome proliferator-activated receptor （PPAR-γ） ligand rosiglitazone （RGZ） on human ovarian serous cystadenocarcinoma cell line SKOV3. [Methods] The subcutaneous ovarian cancer SKOV3 xenograft model was established in nude mice. The effect of different doses RGZ on the volume of xenograft tissues was observed. The morphological changes of xenograft tissues were observed by HE staining. The expressions of Bcl-2 and Cytochrome C protein in xenograft were detected by immunohistochemistry. [Results] The volumes of xenograft tissues in RGZ group （4mg/kg,12mg/kg,60mg/kg,120mg/kg） were 0.190± 0.023mm^3,0.065±0.003mm^3,0.195±0.004mm^3 and 0.182±0.023mm^3,respectively,compared with the control group （0.300±0.016mm^3）,the volumes decreased with significant difterence （P〈0.05）. Tumor inhibition rates were 36.7%, 78.3%, 35.0% and 40.0% in RGZ 4mg/kg, 12mg/kg, 60mg/kg, 120mg/kg group respectively. The degeneration of the tumor cells,single-cell death and a large area of coagulation necrosis were observed by HE staining. The expressions of Bcl-2 in the RGZ groups （60mg/ kg, 120mg/kg） were significantly down-regulated compared with the control group,the expressions of Cytochrome C in the RGZ groups （60mg/kg,120mg/kg） were significantly up-regulated compared with the control group （P〈0.05）. [Conclusion] RGZ has obvious inhibition function on the nude mice xenograft and promotes the apoptosis. It suggests that PPAR-γ might be a novel therapeutic target for ovarian cancer.

关 键 词：卵巢癌 罗格列酮 过氧化物酶体增殖物激活受体-γ配体 BCL-2 细胞色素C 

分 类 号：R737.31[医药卫生—肿瘤]