干扰素α体外逆转烷化剂马法兰耐药的研究

REVERSAL OF MELPHALAN RESISTANCE BYINTERFERON αIN VITRO

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。

AbstractTwo melphalan (Mel) resistant leukeniic cell lines,K562/Mel, L1210/Mei were established. Interferon aat 500IU/ml is nontoxic to both cell lines , but the cyto-toxicity of Mel is potentiated 3. 7 and 2. 1 fold in L1 210/Mel and K562/Mel respectively by it. Although inter-feron-a does not act as an inhibitor of total GST activity ,it does cause significant decrease in the expression levelof an a class of GST gene. These results provide furtherevidence that GST a may be involved in the developmentof resistance to bifunctional alkylating agents and sug-gest that interferona may be of value as an adjuvant toBMT condition regimen in some patients with tumors re-sistant to alkylating agents.Wey words IFN-a Melphalan Reversal of re-slstance