HL-60/VCR多药耐药细胞株耐药机制的研究

背景与目的：白血病细胞对化疗药物的耐药是白血病治疗失败的主要原因,多药耐药细胞株为白血病多药耐药机制和逆转多药耐药性的研究提供了良好的模型。为探讨药物诱导产生多药耐药机制,我们对HL-60/VCR细胞的耐药机制进行了研究。方法：应用流式细胞术和一组抗体,对药物敏感细胞株HL-60和多药耐药细胞株HL-60/VCR细胞的耐药相关蛋白P-gp、MRP、LRP、BCRP、GST-π,以及凋亡调节蛋白bcl-2、bax、bcl-x、bad的表达进行分析。结果：在HL-60/VCR细胞株中,耐药相关蛋白P-gp、MRP、BCRP、GST-π分别是其在HL-60细胞株中的18.62、1.19、1.50、1.32倍,而LRP无变化。凋亡抑制蛋白bcl-2、bcl-x分别是其在HL-60细胞株中的2.48、1.25倍,凋亡调节蛋白bad是HL-60细胞株中的1.08倍;而凋亡诱导蛋白bax反而降低,是HL-60细胞株中的0.88倍。结论：多种机制参与HL-60/VCR的多药耐药,涉及耐药蛋白P-gp、MRP、BCRP和GST-π的表达增强,而且凋亡调节蛋白bcl-2、bax、bcl-x、bad均可能参与其耐药机制的形成。

Multidrug resistance mechanisms in cell line HL-60/VCR

BACKGROUND & OBJECTIVE: Drug resistance is a major factor in chemotherapeutic failure of leukemia. Multidrug resistant cell lines are the good models for investigating the mechanisms and reversal of acquired drug resistance. This study was designed to explore the multidrug resistance (MDR) mechanisms in cell line HL-60/VCR. METHODS: Flow cytometry and a panel of antibodies were used to analyze the expression of MDR proteins (P-gp, MRP, LRP, BCRP, GST-pi) and apoptosis-modulating proteins (bcl-2, bcl-x, bax, bad) in MDR cell line HL-60/VCR and drug sensitive cell line HL-60. RESULTS: The expression levels of MDR proteins (P-gp, MRP, BCRP, GST-pi) were (18.62, 1.19, 1.50, 1.32-flod) higher in HL-60/VCR than in HL-60, while the expression of LRP level was similar. The levels of apoptosis-modulating proteins(bcl-2, bcl-x, bad) were (2.48, 1.25, 1.08-fold) higher in HL-60/VCR than in HL-60, while the pro-apoptosis protein bax contrarily decreased in HL-60/VCR. CONCLUSION: Various MDR mechanisms were involved in multi-drug resistance HL-60/VCR cell line, which including increasing expression of drug-resistance protein (P-gp, MRP, BCRP, and GST-pi); the apoptosis-modulating proteins (bcl-2, bcl-x, bax, and bad) might take part in the mechanism of drug resistance.