Elucidation of molecular mechanism for chemoresistance elicited by lipid peroxide-detoxifying enzymes.

醛酮还原酶（AKR）1B10的上调与人结肠癌HT 29细胞对阿霉素或丝裂霉素C的耐药性发展有关。此外，两种耐药癌细胞的几项实验结果表明，AKR1B10的高表达通过促进还原酶对药物的活性和抗氧化活性而有助于化学抗性的机制。此外，非耐药细胞中酶的过表达和抑制分别降低和增加了对药物细胞毒性作用的敏感性，提高了AKR1B10是参与结肠癌化疗耐药性获得的主要因素的可能性。

Up-regulation of aldo-keto reductase (AKR) 1B10 was provoked with resistance development of human colon cancer HT29 cells toward doxorubicin or mitomycin C. In addition, results in several experiments with the two resistant cancer cellssuggest that the high AKR1B10 expression contributes tomechanism(s) of the chemoresistance through facilitating the reductase activity toward the drugs and antioxidant activity. Furthermore, overexpression and inhibition of the enzyme in the non-resistant cells decreased and increased, respectively, susceptibility to cytotoxic effects of the drugs, raising the possibility that AKR1B10 is a predominant factor involved in gain of colon cancer chemoresistance.