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Synergistic effects of nimesulide and 5-fluorouracil on tumor growth and apoptosis in the implanted hepatoma in mice

机译:尼美舒利和5-氟尿嘧啶对小鼠肝癌移植瘤生长和凋亡的协同作用

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AIM: To compare the effect of nimesulide or/and 5-fluorouracil (5-FU) on tumor growth inhibition and apoptosis in mice with the implanted hepatoma and to observe their possible interactions. METHODS: The inhibitory effects on tumor growth was evaluated by inhibition rate. Apoptosis was assessed by the ultrastructural, flow cytometry features and the DNA ladder demonstrated by agarose gel electrophoresis. PGE_2 level was determined by radioimmunoassay. Expression levels of c-jun, c-fos and p53 were evaluated by western blotting. RESULTS: Nimesulide or 5-FU alone inhibited the growth of hepatoma, while a synergistic effect was observed for a combined use of both. More pronounced morphologic changes for tumor cell apoptosis and the DNA ladder were found for the latter treatment. Expression levels of c-jun and p53 were found to be elevated for the tumors from mice treated with nimesulide and 5-FU comparing to those with either of them, but a reduced PGE_2 level was observed only for the treatment with nimesulide. No change was detected on c-fos expression. CONCLUSION: Nimesulide and 5-FU appear to have synergistic effects for the growth inhibition and apoptosis induction. Both were found to be overexpressed in p53 and c-jun proteins, rather than that of c-fos, associations with the resulted apoptosis.
机译:目的:比较尼美舒利或5-氟尿嘧啶(5-FU)对移植有肝癌的小鼠肿瘤生长的抑制和凋亡的作用,并观察其可能的相互作用。方法:通过抑制率评价其对肿瘤生长的抑制作用。通过超微结构,流式细胞术特征和通过琼脂糖凝胶电泳证明的DNA阶梯来评估凋亡。通过放射免疫测定法测定PGE_2水平。通过蛋白质印迹法评估c-jun,c-fos和p53的表达水平。结果:单独使用尼美舒利或5-FU可抑制肝癌的生长,而将两者联合使用可观察到协同效应。对于后一种治疗,发现了肿瘤细胞凋亡的更明显的形态学改变和DNA梯。发现用尼美舒利和5-FU治疗的小鼠的肿瘤中c-jun和p53的表达水平均高于使用它们的小鼠,但是仅用尼美舒利治疗观察到PGE_2水平降低。在c-fos表达上未检测到变化。结论:尼美舒利和5-FU似乎具有抑制生长和诱导细胞凋亡的协同作用。发现两者均在p53和c-jun蛋白中过度表达,而不是在c-fos蛋白中过度表达,这与导致的细胞凋亡相关。

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