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LY294002与化疗药物联用对白血病K562细胞多药耐药的逆转作用
引用本文:张晔,曲秀娟,刘云鹏,荆薇,侯科佐,滕月娥,张敬东. LY294002与化疗药物联用对白血病K562细胞多药耐药的逆转作用[J]. 中国癌症杂志, 2008, 18(11)
作者姓名:张晔  曲秀娟  刘云鹏  荆薇  侯科佐  滕月娥  张敬东
作者单位:中国医科大学附属第一医院肿瘤内科,辽宁,沈阳,110001
基金项目:国家自然科学基金,辽宁省科技攻关项目
摘    要:背景与目的: 传统逆转白血病多药耐药的药物由于不良反应大而限制了其在临床中的应用,进一步研究白血病多药耐药产生机制和有效逆转靶点成为攻克白血病多药耐药的关键.为此,本研究探讨LY294002[磷脂酰肌醇-3-激酶(P13-K/Akt)通路抑制剂]对人类白血病K562细胞多药耐药的逆转作用.方法: 锥虫蓝拒染法测定细胞生长增殖.Western印迹榆测K562/S和K562/D细胞中P-gp及p-Akt的表达.流式细胞术检测细胞内药物积聚.结果: K562/D细胞对柔红霉素(DNR)、多柔比星(ADR)、长春新碱(VCR)、依托泊苷(VP16)交叉耐药,相对其亲本细胞的耐药倍数分别为65、52、134和50.DNR诱导了K562/D细胞的P-gp、p-Akt过度表达.LY294002使K562/D细胞内药物积聚增加,部分逆转了K562/D细胞对DNR、ADR、VCR、VP16的耐药性(相对耐药倍数降至23、21、63和29),而对敏感细胞K562/S的耐药性无影响. 结论:LY294002部分逆转K562/D细胞的多药耐药,可能于DNR诱导K562/D细胞的P-gp、p-Akt过度表达而LY294002抑SUP13-K/Akt信号转导通路有关.

关 键 词:白血病  多药耐药

Effect of LY294002 and its combination with chemotherapy drugs on the proliferation of human leukemia K562 cell line and its possible mechanism
ZHANG Ye,QU Xiu-juan,LIU Yun-peng,JING Wei,HOU Ke-zuo,TENG Yue-e,ZHANG Jing-dong. Effect of LY294002 and its combination with chemotherapy drugs on the proliferation of human leukemia K562 cell line and its possible mechanism[J]. China Oncology, 2008, 18(11)
Authors:ZHANG Ye  QU Xiu-juan  LIU Yun-peng  JING Wei  HOU Ke-zuo  TENG Yue-e  ZHANG Jing-dong
Affiliation:ZHANG Ye QU Xiu-juan LIU Yun-peng JING Wei HOU Ke-zuo TENG Yue-e ZHANG Jing-dong (Department of Medical Oncology,the First Hospital,China Medical University,Shenyang Liaoning 110001,China)
Abstract:Background and purpose:Remarkable advances have been made in cancer chemotherapy by developing new anticancer drugs and therapy strategies.However,multidrug resistance in human cancers remains a major clinical challenge for cancer treatment.Attempts in several clinical studies to reverse multidrug resistance protein (MDR) by using MDR modulators have not yet generated promising results.Our aim was to explored the mechanism of reversal of multidrug resistance in human leukemia K562 cells by PI3-K inhibitor.M...
Keywords:P13-KAkt
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