中文摘要：

背景与目的：磷脂酰肌醇3-激酶／蛋白激酶B[phosphatidylinositol-3-kinase（P13-K）／proteinkinaseB（Akt），P13-K／Aktl通路是调控细胞生存的重要信号转导通路之一。本研究旨在探讨P13-K抑制剂LY294002对P-gP过表达的人类白血病K562／DNR和胃癌SGC7901／ADR细胞多药耐药性的逆转作用。方法：将细胞分为单纯药物组和LY294002预处理组，单纯药物组分别以柔红霉素（daunorubicin，DNR）、阿霉素（adriamycin，ADR）、长春新碱（vincristine，VCR）和依托泊甙（etoposide，VP-16）处理，LY294002预处理组在加药前以LY294002进行预处理。用台盼蓝拒染法及MTT法检测药物敏感性及LY294002对细胞耐药性的影响。Westernblot检测K562／DNR和SGC7901／ADR细胞中P．gP及p-Akt的表达。流式细胞术检测细胞内药物浓度。结果：2．5μmol／LLY294002预处理显著降低DNR、ADR、VCR和VP-16对K562／DNR细胞的IC50，相对逆转效率分别为72．4％、64．9％、60．4％和52．8％。此外，LY294002部分逆转SGC7901／ADR对ADR的耐药性，相对逆转效率为31．0％。LY294002预处理可部分抑制p-Akt和P-gP的表达。随着处理时间的延长．K562／DNR、SGC7901／ADR细胞内DNR、ADR的蓄积效应有增强的趋势。结论：LY294002通过抑制P13-K／Akt信号转导通路，部分逆转P-gp介导的白血病和胃癌细胞的多药耐药。

英文摘要：

Background and Objective： Phosphatidylinositol-3-kinase/protein kinase B （PI3-K/Akt） signaling pathway plays an important role in cell survival. This study was to explore the reversal effect of PI3-K inhibitor LY294002 on P-glycoprotein （P-gp）-mediated multidrug resistance （MDR）in human leukemia cell line K562/DNR and gastric cancer cell line SGC7901/ADR. Methods. The cells were divided into simple drug-treated groups and LY294002-pretreated groups： the former groups received treatment of daunorubicin （DNR）, adriamycin （ADR）, vincristine （VCR） and etoposide （VP-16）, respectively, the latter groups received pretreatment of LY294002 before drug treatment. Trypanblue dye exclusion method and MTT assay were used to detect the drug sensitivity of K562/DNR and SGC7901/ADR cells, and the effect of LY294002 on drug resistance. The expression of P-gp and phosphorylated Akt （p-Akt） in K562/DNR, SGC7901/ADR, and their parental cell lines K562 and SGC7901 was detected by Western blot. Intracellular drug accumulation was measured by flow cytometry （FCM）. Results. LY294002 pretreatment significantly decreased the 50% inhibition concentration （IC50） of DNR, ADR, VCR and VP-16 for K562/DNR cells, with reverse efficiencies of 72.4%, 64.9%, 60.4% and 52.8%, respectively. In SGC7901/ADR cells, the similar result was obtained with a reverse efficiency of 31.0%. LY294002 pretreatment partially inhibited the expression of p-Akt and P-gp, and promoted the intracellular accumulation of DNR and ADR in K562/DNR and SGC7901/ADR cells, respectively. Conclusion： LY294002 could partially reverse MDR in K562/ DNR and SGC7901/ADR cells in vitro via inhibiting PI3-K/Akt pathway.