LY294002对人乳腺癌细胞株MCF7ADR耐药逆转作用.docVIP

LY294002对人乳腺癌细胞株MCF7ADR耐药逆转作用 　　[摘要] 目的 探讨PI3K/Akt信号转导通路特异性阻滞剂LY294002在体外对人乳腺癌细胞株MCF-7/ADR的耐药逆转作用。方法 乳腺癌细胞MCF-7和MCF-7/ADR各自分为未加LY294002的对照组及加入不同浓度的LY294002组,MTT法观察各组药物的细胞毒作用。选用流式细胞术(FCM)检查细胞凋亡率、细胞分布周期的变化。结果 ①LY294002在浓度10μmol/L以下时对两种细胞基本无毒性,为安全有效的逆转剂量。②阿霉素对MCF-7和耐药细胞MCF-7/ADR的半数抑制浓度(IC50)分别为(0.14±0.02)μmol/L和(15.74±0.08)μmol/L,耐药倍数为112倍。③LY294002能够增强阿霉素对MCF-7/ADM的细胞毒作用,LY294002浓度0.1、2.5、5.0、10μmol/L分别作用于 MCF-7/ADM细胞48h后,耐药细胞株的IC50分别降至(13.53±0.10)μmol/L、(10.24±0.08)μmol/L、(5.53±0.16)μmol/L、(2.29±0.12)μmol/L,差异有统计学意义(P0.01)。④LY294002可显著增加MCF-7/ADR细胞凋亡率(P0.01)。细胞周期分布显示,加用LY294002对各个细胞周期影响不明显。结论 LY294002能够增加MCF-7和MCF-7/ADR的化疗敏感性,部分逆转耐药细胞MCF-7/ADR的多药耐药性。 　　[关键词] 乳腺癌;LY294002;多药耐药;逆转 　　[中图分类号] R737.9 [文献标识码] A [文章编号] 1673-9701(2010)06-17-03 　　 　　Reverse Effect of LY294002 on Multidrug Resistance of Human Breast Cancer Cell Line MCF-7/ADR 　　GAO Li1ZHAO Ying2 　　1.Shanxi Medical University,Taiyuan 030001,China; 2.Department of General Surgery,the First Hospital of Shanxi Medical University,Taiyuan 030001,China 　　 　　[Abstract] Objective To investigate the reverse effect of LY294002(a specific inhibitor of the signaling pathway PI3K/Akt) on the multidrug resistance of human breast cancer cell line MCF-7/ADR. Methods MCF-7 and MCF-7/ADR cells were treated with different concentrations of LY294002(LY294002 group)or without LY294002(control group). The drug cytotoxicity was detected by MTT and the apoptosis and cell cycle distribution were evaluated by flow cytometry in each group. Results ①LY294002 at a concentration of less than 10μmol/L had no obvious cell toxicity on MCF-7 and MCF-7/ADR cells,showing the concentration of LY294002 was a safe and effective reverse dose. ②The half inhibitory concentration(IC50) of ADM to MCF-7 and MCF-7/ADR cells was(0.14±0.02)μmol/L and(15.74±0.08)μmol/L, respectively, and the drug-resistant index of MCF-7/ADR was 112. ③LY294002 could enhance ADM cytotoxicity on MCF-7/ADR,and after LY294002 at the concentrations of 0.1,2.5,5.0 and 10μ