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LY294002对人乳腺癌细胞株MCF-7/ADR的耐药逆转作用

Reverse Effect of LY294002 on Multidrug Resistance of Human Breast Cancer Cell Line MCF-7/ADR
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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(P<0.01)。④LY294002可显著增加MCF-7/ADR细胞凋亡率(P<0.01)。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。 Objective To investigate the reverse effect of LY294002（a specific inhibitor of the signaling pathway PI3K/Akt） on the muhidmg 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 MTF 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（ICs0） 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 10 μmol/L respectively acted on MCF-7/ADR for 48 hours,the resistant cell line IC50 was reduced to（13.53 ±0.10）μmol/L,（10.24±0.08）μmol/L,（5.53 ± 0.16 ） μmol/L and（2.29 ±0.12）IXmol/L, respectively（P〈0.01 ）. ④LY294002 significantly increased the apoptosis rate of MCF-7/ADR（P〈0.01）. LY294002 had no obvious effect on the cell growth cycle. Conclusion LY294002 is able to increase the sensitivity of MCF-7 and MCF-7/ADR to chemotherapy and partially reverse the muhidrug resistance of MCF-7/ADR.
作者 高丽 赵瑛
机构地区 山西医科大学 山西医科大学第一医院普外科
出处 《中国现代医生》 2010年第6期17-19,共3页 China Modern Doctor
关键词 乳腺癌 LY294002 多药耐药 逆转 Breast cancer LY294002 Multidrug resistance Reverse
分类号 R737.9 [医药卫生—肿瘤]
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参考文献9

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二级参考文献5

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中国现代医生
2010年 第6期

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