内皮抑素抑制膀胱癌皮下移植瘤生长及其机制的初步探讨  

The influences of endostatin on bladder tumor growth and its mechanism

作　　者：侯树坤[1] 杜志军[1] 王晓峰[1] 闫征[2] 顾永鹏[1] 叶海云[1] 

机构地区：[1]北京大学人民医院泌尿外科,100044 [2]北京大学人民医院中心实验室,100044

出　　处：《中华泌尿外科杂志》2002年第10期590-593,共4页Chinese Journal of Urology

基　　金：国家自然科学基金 (3 0 0 70 75 4)

摘　　要：目的　探讨人内皮抑素对膀胱癌EJ细胞生长的作用及机制。　方法　 (1)体外实验观察内皮抑素对血管内皮细胞 (ECV30 4 )和膀胱癌EJ细胞生长的影响 ;(2 )EJ细胞移植入裸鼠皮下 ,观察内皮抑素对裸鼠皮下瘤生长情况的影响 ;(3)应用WesternBlot和RT PCR法观察皮下瘤组织中MMPs和TIMP 2的表达。　结果　 (1)内皮抑素具有抑制bFGF刺激后的内皮细胞ECV30 4及抑制EJ细胞增殖的作用 (P≤ 0 .0 5 ) ;(2 )治疗组皮下肿瘤质量 (0 .70± 0 .16 ) g ,对照组为 (1.14± 0 .2 1) g ,两组比较 ,差别有显著性意义 (P <0 .0 5 ) ;(3)人内皮抑素抑制裸鼠皮下膀胱癌瘤MMP 9mRNA表达 ,对MMP 2、TIMP 2、MT1 MMPmRNA表达无影响 ;(4)瘤组织中未检测到MMP 2、MMP 9和TIMP 2蛋白。　结论　人内皮抑素具有抑制膀胱肿瘤生长的作用 ,其作用机制与抑制MMPObjective To evaluate the inhibitory effect of endostatin on bladder tumor and to investigate the possible mechanism of the inhibition. Methods (1)By means of MTT method,the effects of endostatin on ECV304 and EJ cells proliferation were studied.(2)Ten nude mice were subcutaneously implanted with EJ bladder tumor cells (1×10 7/ml). After the tumor volume exceeded 100～200 mm 3,the mice were randomized into two groups.One group received recombinant human endostatin (2 mg·kg -1 ·d -1 ) whereas the other group received PBS as control.All the treatment lasted 21 days.(3) After that,the mice were sacrificed and then MMPs and TIMPs mRNA expression were measured in implanted tumor by RT PCR and Western blot method. Results (1)Endostatin inhibits ECV304 proliferation stimulated with bFGF (5 ng/ml).In addition,we report for the first time that endostatin also inhibits EJ cells proliferation.(2)The mean tumor weight of endostatin treated group (0.70±0.16 g) was significantly lower than that of control group (1.14±0.21)g, P <0.05.(3)MMP 9 mRNA expression was inhibited in endostatin treated group,but MMP 2,TIMP 2 and MT1 MMP mRNA were not influenced. Conclusions These results demonstrate that endostatin has its antitumor effects on bladder carcinomas,and that at least in part,the important mechanisms of endostatin action on the potent antiangiogenic and antitumor activities involves regulating the MMPs,TIMPs expression.

关 键 词：内皮抑素 抑制 膀胱癌 皮下移植瘤 

分 类 号：R737.14[医药卫生—肿瘤]