Ciglitazone对肝癌血管形成的抑制作用  

To Investigate the Iffect of PPARγ' s Ligand on Tumor Aangiogenesis and its Mechanisms

作　　者：张万广[1] 严斌[1] 陈孝平[1] 侍作亮[1] 张志伟[1] 张必翔[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肝脏外科中心,武汉430030

出　　处：《中国分子心脏病学杂志》2006年第4期219-222,F0003,共5页Molecular Cardiology of China

基　　金：国家自然科学基金项目资助(30400431)

摘　　要：目的探讨过氧化物酶体增殖物激活受体配体(ciglitazone)在肝癌血管形成中的抑制作用及bcl-2的表达变化。方法3周龄裸鼠随机分为处理组(10只)、对照组(10只)。皮下接种HepG2肝癌细胞,待肿瘤生长至0．5 cm时,处理组瘤内注射100μmol／L的ciglitazone 100μl,对照组注射100μl生理盐水,隔天1次,连续15次。免疫组化法和免疫印记法(Western blot)测定癌组织中因子VIII、VEGF和bcl-2的表达。结果处理组的肿瘤体积小、生长慢于对照组,为(2．51±0．33)g vs(3．44±0．40)g,但处理组PPARγ的表达,与对照组相比无明显差异,处理组裸鼠体内肿瘤微血管密度(MVD)低于对照组[(7．8±1．9)vs(16．9±1．2),P<0．05],VEGF的表达处理组与对照组相比为(0．149±0．057)vs(0．433±0．105),两者具有显著性差异。bcl-2表达处理组较对照组相比(0．435±0．127)vs(0．261±0．114),处理组bcl-2的表达为正常组的1．79倍。结论Ciglitazone对肝癌血管形成具有抑制作用,分析其机制可能与Ciglitazone增加凋亡抑制蛋白bcl-2的表达有关。Objective To investigate the effect of PPARγ＇ s ligand on tumor angiogenesis and its mechanisms. Methods HepG2 cells were inoculated subcutaneously into 20 nude mice, which were randomly divided into two groups： the control group, the ciglitazone group. The weights of subcutaneous tumors were detected. The expression of VIII factor was analyzed by Immohistochemistry （IHC）. The expression of VEGF and bcl-2 were analyzed by Western blot. Results Direct injection of ciglitazone into HepG2-induced tumors could suppress tumor growth in nude mice. The expression of VIII factor and VEGF decreased significantly in ciglitazone group compared with control group. But the expression of bcl-2 increased in ciglitazone group compared with control group. Conclusions Ciglitazone could inhibit HepG2 proliferation and angiogenesis in vivo, and the mechanism may be due to the fact that it can induce the expression of bcl-2.

关 键 词：CIGLITAZONE 过氧化物酶体增殖物激活受体Γ 肝癌 血管生成 BCL-2 

分 类 号：R735.7[医药卫生—肿瘤]