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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。
OBJECTIVE: To observe the effect of nimesulide on tumor-bearing inhibition and apoptosis in mice and to explore its possible molecular mechanism. Methods: Male mice were given nimesulide 10mg / kg, 20mg / kg and 40mg / kg each for 21 days. The effect of nimesulide on tumor cell apoptosis was observed by electron microscopy, flow cytometry and agarose gel electrophoresis , The content of PGE_2 in tumor tissue was determined by radioimmunoassay and the expression of COX-2, c-myc, Bax and Bcl-2 were detected by Western blot.Results: Nimesulide can inhibit the tumor growth of mice in a dose-dependent manner % To 62%), the apoptosis rate induced by nimesulide was (51.3 ± 1.5)% at high dose, the change of DNA “trapezoid” was more obvious and the content of PGE_2 was significantly lower. Western blot showed that the apoptosis rate of COX-2 and Bcl- Decreased expression, increased Bax expression, c-myc no change. Conclusion: The inhibitory effect of nimesulide on tumor-bearing hepatocellular carcinoma may be related to the inhibition of COX-2, the decrease of PGE 2 content and the up-regulation of Bax / Bcl-2 ratio to induce tumor cell apoptosis.