Nimesulide inhibits tumor growth in mice implanted hepatoma: overexpression of Bax over Bcl-2  

尼美舒利抑制小鼠荷瘤肝癌的生长:提高Bax/Bc 1-2表达的比值(英文)

作　　者：李晓红[1] 李俊杰[2] 张海伟[3] 孙鹏[1] 张艳玲[1] 蔡绍晖[1] 任先达[1] 

机构地区：[1]暨南大学药学院药代动力学教研室 [2]附属华侨医院临床药理研究室 [3]医学院病理教研室

出　　处：《Acta Pharmacologica Sinica》2003年第10期1045-1050,1063,共7页中国药理学报（英文版）

基　　金：Project supported by the Overseas Chinese Affairs Office of the State Council Foundation, № 39770300.

摘　　要：AIM: To investigate whether nimesulide could suppress tumor growth and induce apoptosis in implanted hepatoma mice and to explore the molecular mechanisms. METHODS: Male mice received nimesulide 10mg/kg, 20mg/kg, and 40mg/kg ig daily for 21d. Electron microscopy(EM), flow cytometry(FCM), DNA ladder, radioimmunoassay(RIA), and Western blot analysis were employed to investigate effect of nimesulide on mice hepatoma and the related molecular mechanisms. RESULTS: Nimesulide inhibited the growth of hepatoma(from 14% to 62%) and elicited typical apoptotic morphologic changes. The DNA ladder of high dose nimesulide was more clearly observed and apoptotic rate was 51.3%±1.5%. Nimesulide also decreased cyclooxygenase-2(COX-2), prostaglandin E_2(PGE_2) and Bcl-2 expression, while increased the level of Bax protein. CONCLUSION: Nimesulide supresses tumor growth and induces apoptosis by inhibiting COX-2 and PGE_2 expression, which may be related to overexpression of Bax over Bcl-2.目的:观察尼美舒利对小鼠荷瘤抑制和凋亡诱导作用并探讨其可能的分子机制。方法:雄性小鼠给予尼美舒利10mg/kg,20mg/kg和40mg/kg各灌胃21天,用电镜,流式细胞术,琼脂糖电泳观察尼美舒利诱导肿瘤细胞凋亡的作用,放射免疫法测定瘤组织PGE_2含量,Western blot观察COX-2,c-myc,Bax和Bcl-2的表达.结果:尼美舒利能抑制小鼠荷瘤生长,且具有剂量依赖性(14％到62％),高剂量时,尼美舒利诱导的细胞凋亡率是(51.3±1.5)％,DNA“梯形”变化更加明显,PGE_2含量明显降低,Westernblot显示COX-2和Bcl-2表达降低,Bax表达增加,c-myc无变化。结论:尼美舒利对荷瘤肝癌的抑制作用可能与抑制COX-2而降低PGE_2含量和上调Bax/Bcl-2比值诱导瘤细胞凋亡有关。

关 键 词：NIMESULIDE cyclooxygenase inhibitors PROSTAGLANDINS apoptosis liver neoplasms 

分 类 号：R735.7[医药卫生—肿瘤] R971.1[医药卫生—临床医学]