非甾体类抗炎药对荷瘤小鼠肝癌的促凋亡作用(英文)  

Non-steroidal anti-inflammatory drugs induce apoptosis in implanted hepatoma in mice

作　　者：吴伟江[1] 李晓红[2] 任先达[2] 罗羽宏 周其京 梁晓宇 

机构地区：[1]暨南大学附属华侨医院普外科,广东广州510632 [2]暨南大学药学院药代动力学教研室,广东广州510632 [3]龙川县人民医院普外科,广东龙川517300

出　　处：《中国病理生理杂志》2003年第8期1074-1078,共5页Chinese Journal of Pathophysiology

基　　金：SupportedbytheOverseasChineseAffairsOfficeoftheStateCouncilFoundation (No 98- 33) ;NationalNaturalScienceFoundationofChina (No .39770 30 0 )

摘　　要：目的 :探讨非甾体类抗炎药 (NSAIDs)中选择性及非选择性的环氧化酶 - 2抑制剂对小鼠移植的肝肿瘤的凋亡诱导作用和其分子机理。方法 :昆明种小鼠腋下无菌接种腹水保种的鼠肝癌H2 2细胞 ,给予布洛芬 ,吲哚美辛和尼美舒利灌胃每天 1次 ,2 1d后断颈法处死小鼠 ,应用电镜 ,DNAladder,流式细胞术及Westernblot等方法研究NSAIDs对小鼠荷瘤的作用及分子机理。结果 :3种药均能诱导Hep2 2肿瘤细胞的凋亡 ,与对照组 (3.3%± 0 .6 % )相比 ,布洛芬 ,吲哚美辛和尼美舒利的细胞凋亡率分别上升为 15 %± 1.0 % ,2 9.7%± 1.5 %和 4 6 .3%± 3.5 %。尼美舒利治疗组呈现更为明显的凋亡形态和DNA梯度 ,也明显下调bcl-xL和bcl- 2的表达 ,而吲哚美辛和布洛芬下调bcl- 2表达的同时上调bcl-xL 的表达。 3种药物都不改变c -myc的表达。结论 :NSAIDs可抑制小鼠肝肿瘤的生长 ,诱导其肿瘤细胞调亡 ,其中选择性COX - 2抑制剂尼美舒利的作用最为明显 ,并与调节bcl-xL和bcl- 2的表达有关。AIM: To study the mechanism of the effect of NSAIDs on apoptosis in mice hepatoma at anti-inflammatory doses. METHODS: Kunming breed mice were inoculated subcutaneously in the flank with mice hepatoma H22 cell line. The effects of ibuprofen, indomethacin, and nimesulide on apoptosis were determined by using electron microscopy, agarose gel electrophoresis, flow cytometry, and Western blot analysis of the expression of c-myc, bcl-x_L and bcl-2 proteins. RESULTS: NSAIDs induced apoptosis of mice implanted hepatoma, which includes the morphological changes such as reduction in the volume, and the nuclear chromatin condensation, as well as the “ladder pattern' revealed by agarose gel electrophoresis of DNA. The apoptotic index was increased to 15.0%±1.0%, 29.7%±1.5%, 46.3%±3.5% from 3.3%±0.6% by detecting Sub-G_1 peaks on flow cytometry. Western blot analysis showed that levels of bcl-2 and bcl-x_L were significantly reduced by treatment with nimesulide. Ibuprofen and indomethacin decreased bcl-2 expression but increased bcl-x_L expression. C-myc wasn't changed in these groups. CONCLUSION: These results suggest that NSAIDs induce apoptosis of mice hepatoma, which may be due to their regulation on the expressions of bcl-2 family genes.

关 键 词：消炎药 非甾类 电泳 琼脂凝胶 细胞凋亡 肝肿瘤 

分 类 号：R735.7[医药卫生—肿瘤]