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在两株对烷化剂马法兰(Mel)耐药的白血病细胞系L1210/Mel及K562/Mel中,我们发现无细胞毒性剂量的干扰素。(IFN-α)能明显逆转Mel耐药。在该两个耐药细胞系中,Mel杀伤率被IFN-α分别增强3.7倍及2.1倍,其效果优于国际上常用烷化剂耐药逆转剂利尿酸(EA)。其逆转机制与EA不同,IFN-α不能抑制谷恍甘肽-S-转移酶(GST)总活性,却能够特异性降低GST-α基因的表达水平。这一研究结果表明,干扰素-α可作为骨髓移植预处理方案的辅助药物以增强烷化剂对肿瘤细胞的清除率,并且为GSTα参与烷化剂Mel的耐药机制提供进一步证据。
In two leukemia cell lines, L1210 / Mel and K562 / Mel, both alkylating agents melphalan, we found a noncytotoxic dose of interferon. (IFN-α) can significantly reverse the resistance of Mel. In these two drug-resistant cell lines, the killing rate of Mel was enhanced by 3.7 times and 2.1 times respectively by IFN-α, which is better than the commonly used international alkylating agent reversal agent, uric acid (EA). The reversal mechanism is different from EA, IFN-α can not inhibit the total activity of glutathione-S-transferase (GST), but can specifically reduce the expression of GST-α gene. The results of this study indicate that interferon-α can be used as adjunct to bone marrow transplantation to enhance the clearance rate of alkylating agents to tumor cells and provide further evidence that GSTα participates in the resistance mechanism of alkylating agent Mel.