In vitro study on cytotoxicity of combination of some chemotherapy reagents towards arsenic trioxide-resistant leukemic cells

Abstract

Abstract: AIM: To explore the cytotoxicity of combination of some chemotherapy reagents towards K562/AS2, an arsenic trioxide (As2O3)-resistant leukemic cell line.METHODS: MTT assay was used to detect the cytotoxicity, and the combined drug effect of two drugs was analyzed with Chou-Talalay Combination Index (CI). Flow Cytometry was used to detect the P-glycoprotein on the cell surface and the introcellular concentration of daunorubicin (DNR).RESULTS: The relative resistant folds of K562/AS2 cell line to As2O3, DNR, VP16, harringtonine (H), NVT and Ara-cwere 7.4, 2.9, 3.8 and 1.1, respectively.The fluorescence of the P-glycoprotein on the surface or of the DNR inside the cells detected was not significantly different between the K562 and the K562/A02 cell line (P >0.05).The combination indexes of As2O3 combined with DNR, VP16, H or NVT to K562, K562/AS2 and K562/A02 cell lines were all above 1.The combination indexes of Verapamil combined with DNR to both K562 and K562/AS2 cell lines were above 1, and to the K562/A02 were below 1.CONCLUSION: K562/AS2 cell line is resistant to As2O3, DNR, VP16 and NVT.The mechanism of the drug resistance is not associated with the expression of P-gp.Verapamil combined with DNR can reverse the resistance of Pgp expressing leukemia cell, K562/A02, to DNR, but can not reverse the resistance of K562/AS2 cell line.The cytotoxicity of As2O3 combined with DNR, VP16, H and NVT shows antagonism to K562, K562/AS2 and K562/A02 cell lines.

Key words: multidrug resistance, k562 cell line, arsenic trioxide, daunorubicin, etoposide, harringtonine, mitoxantrone, cytarabine, drug interactions

CLC Number:

R979.1

ZHUO Jia-cai, WANG Ming-chun, TAO Xiao-mei, LIMing, YOU Wei-wen, CAI Li-sheng, LIU Huan-xun. In vitro study on cytotoxicity of combination of some chemotherapy reagents towards arsenic trioxide-resistant leukemic cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(9): 1033-1037.

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