P-糖蛋白的表达和功能活性调控研究进展

Advances in the study of expression and regulation of P-glycoprotein

积极外排异物是细胞适应外界环境的主要机制,由此产生的多药耐药是肿瘤化疗失败的首要原因。由MDR1基因编码的P-糖蛋白的高表达导致药物外排增加是MDR发生的主要机制。最近研究发现,转录因子(transcription factor)、DNA甲基化、组蛋白乙酰化程度以及磷酸化、糖基化、泛素化和MDR1基因多态性在P-糖蛋白调控过程中起重要作用,有望成为提高肿瘤化疗效果的治疗新靶点,本文将近年来相关研究进展作一综述。

Resistance to the cytotoxic actions of antineoplastic drugs remains a barrier to the establishment of curative chemotherapy regimens for cancer. Over-expression of P-glycoprotein （P-gp） , encoded by the MDR1 gene is the major molecular mechanism enhancing efflux pump for various anticancer agents, hence caused MDR. Transcription factor, DNA methylation, histone acetylation/deacetylation, phosphorylation and glycosylation and MDR1 gene polymorphisms play pivotal role in regulation of P-glycoprotein, and may become new therapeutic targets. This paper summarized the advances of studies on expression and regulation of P-glycoprotein.