谷胱甘肽-S-转移酶被认为与化疗药物的耐药性有关。这取决于与细胞膜的相互作用。在这项研究中,我们采用磷脂和胆固醇混合物(MIX)的Langmuir单层作为肿瘤细胞膜模型,并研究了它们与抗癌药物顺铂(CDDP)和多柔比星(DOX)的相互作用.我们发现DOX和CDDP都会扩展并影响MIX单层的弹性,但是当加入谷胱甘肽-s-转移酶(GST)及其辅因子谷胱甘肽(GSH)时,这些作用会受到阻碍。DOX或CDDP在MIX/GST/GSH单层的偏振调制红外反射吸收光谱(PM-IRRAS)数据上引起变化,因此表示某种程度的相互作用,不足以改变单层的机械性能。总的来说,本文提供的结果支持了GST灭活DOX和CDDP的假设,并指出了检测和对抗耐药性的可能方向。
Glutathione-s-transferase is believed to be involved in the resistance to chemotherapeutic drugs, which depends on the interaction with the cell membranes. In this
study, we employed Langmuir monolayers of a mixture of phospholipids and cholesterol (MIX) as models for tumor cell membranes and investigated their interaction with the anticancer drugs cisplatin (CDDP) and doxorubicin (DOX). We found that both DOX and CDDP expand and affect the elasticity of MIX monolayers, but these effects are hindered when glutathione-s-transferase (GST) and its cofactor glutathione (GSH) are incorporated. Changes are induced by DOX or CDDP on the polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) data for MIX/GST/GSH monolayers, thus denoting some degree of interaction that is not sufficient to alter the monolayer mechanical properties. Overall, the results presented here give support to the hypothesis of the inactivation of DOX and CDDP by GST and point to possible directions to detect and fight drug resistance.