Ichikawa M, Yoshimura A, Furukawa T, Sumizawa T, Akiyama S
Cancer Research Institute, Faculty of Medicine, Kagoshima University, Japan.
Biochem Biophys Res Commun. 1990 Jan 15;166(1):74-80. doi: 10.1016/0006-291x(90)91913-d.
P-glycoprotein (P-gp) is thought to mediate the transport of anticancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype. P-gp is also expressed in normal human tissues, such as the adrenal gland, kidney, liver, colon and capillary endothelium of the brain. However, the function and transporting substrates of P-gp in normal tissues are still not understood. This paper explains that some compounds in the human plasma can modulate the transporting activity of P-gp. A partially purified fraction from the human plasma enhanced the accumulation of anti-cancer agents in MDR cells. This fraction inhibited the efflux of vinblastine from MDR cells, and also inhibited the photoaffinity labeling of P-gp with azidopine as effectively as vinblastine, quinidine and cepharanthine. The compounds in this purified fraction may be physiological substrates of P-gp and can probably overcome MDR.
P-糖蛋白（P-gp）被认为可介导抗癌药物的转运，并导致多药耐药（MDR）表型。P-gp也表达于正常人体组织，如肾上腺、肾脏、肝脏、结肠以及脑毛细血管内皮。然而，P-gp在正常组织中的功能及转运底物仍不清楚。本文阐述了人血浆中的某些化合物可调节P-gp的转运活性。人血浆中的部分纯化组分增强了抗癌药物在多药耐药细胞中的蓄积。该组分抑制了长春碱从多药耐药细胞中的外排，并且与长春碱、奎尼丁和千金藤素一样有效地抑制了叠氮平对P-gp的光亲和标记。该纯化组分中的化合物可能是P-gp的生理性底物，或许能够克服多药耐药。
