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山东大学学报(医学版)

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表阿霉素、多西紫杉醇、5-氟脲嘧啶序贯对乳腺癌细胞凋亡的影响

阮永威,金星,侯连泽   

  1. 山东大学临床医学院山东省立医院普外科, 山东 济南 250021
  • 收稿日期:2005-09-14 修回日期:1900-01-01 出版日期:2006-07-24 发布日期:2006-07-24
  • 通讯作者: 阮永威

Sequential chemotherapy of Epirubicin,Taxotere,and 5Fluorouracilincreases the apoptosis in breast cancer cell lines

RUAN Yong-wei,JIN Xing,HOU Lian-ze   

  1. Department of General Surgery, Shandong Provincial Hospital, School of Clinical Medicine, Shandong University, Jinan 250021, Shandong, China
  • Received:2005-09-14 Revised:1900-01-01 Online:2006-07-24 Published:2006-07-24
  • Contact: RUAN Yong-wei

摘要: v目的:探讨表阿霉素(epirubicin, Epi)、多西紫杉醇(taxotere, Tax)和5-氟脲嘧啶(5Fluorouracil, 5Fu)序贯对乳腺癌细胞(MCF7)凋亡的影响,为确定最有效的化疗方案提供理论依据。方法:采用硫基碱性蕊香红B(sulphorhodamine B, SRB)法分析3种药物序贯对MCF7的细胞毒作用,中效原则分析药物之间的相互作用,流式细胞仪检测细胞周期和凋亡,Westernblot分析p53、bcl2、bax和p21凋亡相关基因蛋白表达。结果:单一5Fu产生较低细胞毒作用。序贯应用Epi、 Tax有协同作用和增加5Fu的细胞毒效果。序贯应用Epi、Tax导致细胞停滞于G1M期,而5Fu可加快细胞周期或杀死肿瘤细胞,且可使胸腺嘧啶合成酶(TS)表达减少。Epi、Tax和5Fu 序贯应用协同作用更明显(CI<1),同时诱导的MCF7凋亡与雌激素受体(ER)、p53、bcl2、bax状态无关。结论:Epi、Tax和5Fu序贯应用可产生高度协同和时间依赖,实验结果对临床制定最有效化疗方案有重要作用。

Abstract: To evaluate the activity ofhe sequence exposure of Epirubicin(Epi), Taxotere(Tax), and 5Fluorouracil(5Fu) for human breast cancer so as to select the most effective treatment schedule. Methods:The cytotoxic activity of drug on MCF7 was evaluated by sulphorhodamine B assay and the interaction of the different drugs was assessed by median effect principle. The cell cycle and apoptosis were evaluated by flow cytometry. The expressions of p53, bcl2, p21,bax and thymidylate synthase(Ts) were detected by Western blotting. Results:As a single agent, 5Fu exerted a low cytotoxic activity in MCF7 cells. The Epi→Tax sequence induced a synergistic cytocidal effect and enhanced the efficacy of 5Fu. The Epi→Tax sequence blocked MCF7 cells in G2M phase, and the addition of 5Fu forced the cells to progress through cell cycle or killed them. The Epi→Tax sequence induced a significant reduction in basal Ts expression. The sequence of Epi→Tax→5Fu produced a synergistic and highly scheduledependent interaction(CI<1),

Key words: Breast tumour, Epirubicin, Taxus, Sequential chemotherapy, Cell apoptosis

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