Sui H, Fan Z-Z, Li Q
Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Int Med Res. 2012;40(2):426-35. doi: 10.1177/147323001204000204.
Multiple drug resistance (MDR), defined as the ability of tumour cells to survive exposure to many chemotherapeutic agents, is a major cause of treatment failure in human cancers. The membrane transporter P-glycoprotein (Pgp, encoded by the ABCB1 [adenosine triphosphate-binding cassette, subfamily B, member 1] gene) is the main mechanism for decreased intracellular drug accumulation in human MDR cancer. ABCB1/Pgp-mediated MDR involves several signal transduction pathways and transcription factors. Activation of these signal transduction pathways influences the prognosis of MDR human cancer. Signalling pathways involved in ABCB1/Pgp-mediated MDR include the mitogen-activated protein kinase (MAPK), c-Jun NH(2)-terminal kinase (JNK), p38, cyclic adenosine monophosphate-dependent protein kinase, phosphatidylino sitol 3-kinase and protein kinase C signalling pathways. This review summarizes the biological characteristics, target points and signalling cascade mediators of these pathways. Drugs targeted against these pathways may provide new therapies for treatment of ABCB1/Pgp-mediated MDR.
多药耐药性（MDR）被定义为肿瘤细胞在接触多种化疗药物后存活的能力，是人类癌症治疗失败的主要原因。膜转运蛋白P-糖蛋白（Pgp，由ABCB1[三磷酸腺苷结合盒，B亚家族，成员1]基因编码）是人类MDR癌症中细胞内药物积累减少的主要机制。ABCB1/Pgp介导的MDR涉及多种信号转导途径和转录因子。这些信号转导途径的激活影响MDR人类癌症的预后。参与ABCB1/Pgp介导的MDR的信号通路包括丝裂原活化蛋白激酶（MAPK）、c-Jun氨基末端激酶（JNK）、p38、环磷酸腺苷依赖性蛋白激酶、磷脂酰肌醇3激酶和蛋白激酶C信号通路。本综述总结了这些途径的生物学特性、靶点和信号级联介质。针对这些途径的药物可能为ABCB1/Pgp介导的MDR治疗提供新的疗法。
