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目的:探讨化疗药物联合应用对三氧化二砷(As2O3)耐药白血病细胞(K562/AS2)的毒性作用。方法:细胞毒实验采用MTT法,二药合用时细胞毒性作用采用ChouTalalay联合指数法分析,细胞表面P糖蛋白(Pgp)和细胞内柔红霉素(DNR)浓度测定采用流式细胞术测定。结果:K562/AS2细胞对三氧化二砷、柔红霉素、鬼臼乙叉苷(VP16)、三尖杉酯碱(H)、米托蒽醌(NVT)和阿糖胞苷(AraC)的耐药倍数分别为7.4、2.9、3.8、3.6、2.8和1.1。K562细胞和K562/AS2细胞的细胞表面Pgp或细胞内任意荧光强度无显著的统计学意义(P>0.05)。As2O3与DNR、VP16、H或NVT联合应用时,对K562、K562/AS2和Pgp表达的白血病细胞(K562/A02)细胞的联合指数均大于1。异搏定与DNR联合应用时,对K562和K562/AS2细胞的联合指数均大于1,但是对K562/A02细胞的联合指数均小于1。结论:K562/AS2细胞对As2O3、DNR、VP16和NVT耐药,其机制与Pgp表达无关。异搏定联合应用DNR可以逆转K562/A02对DNR的耐药性,不能逆转DNR对As2O3耐药细胞的耐药性。As2O3与DN、VP16、H和NVT联合应用时,对K562、K562/AS2和K562/A02细胞的毒性均为拮抗作用。
Objective: To investigate the toxic effects of chemotherapeutic agents on arsenic trioxide (As2O3) -resistant leukemia cells (K562 / AS2). Methods: Cytotoxicity assay was performed by MTT assay. Cytotoxicity was evaluated by ChouTalalay combined with exponential method. Cell surface P-glycoprotein (Pgp) and intracellular daunorubicin (DNR) concentrations were determined by flow cytometry. Results: The resistance of K562 / AS2 cells to arsenic trioxide, daunorubicin, VP16, harringtonine (H), mitoxantrone (NVT) and cytarabine (AraC) The multiples were 7.4, 2.9, 3.8, 3.6, 2.8 and 1.1, respectively. The cell surface Pgp or intracellular free fluorescence intensity of K562 cells and K562 / AS2 cells was not statistically significant (P> 0.05). When combined with As2O3 and DNR, VP16, H or NVT, the combined index of leukemia cells (K562 / A02) expressing K562, K562 / AS2 and Pgp was greater than 1. When combined with verapamil and DNR, the combined index of K562 and K562 / AS2 cells was greater than 1, but the combined index of K562 / K562 / A02 cells was less than 1. Conclusion: K562 / AS2 cells are resistant to As2O3, DNR, VP16 and NVT, and the mechanism is not related to the expression of Pgp. Verapamil combined with DNR can reverse the resistance of K562 / A02 to DNR, and can not reverse the drug resistance of DNR to As2O3 resistant cells. As2O3 combined with DN, VP16, H and NVT had antagonistic effects on the cytotoxicity of K562, K562 / AS2 and K562 / A02 cells.