P-GLYCOPROTEIN DRUG EFFLUX PUMP INVOLVED IN THE MECHANISMS OF INTRINSIC DRUG RESISTANCE IN VARIOUS COLON CANCER CELL LINES : EVIDENCE FOR A SATURATION OF ACTIVE DAUNORUBICIN TRANSPORT
作者： Ellen C. Spoelstra , Henk Dekker , Gerrit Jan Schuurhuis , Henricus J. Broxterman , Jan Lankelma
DOI: 10.1016/0006-2952(91)90531-9
关键词: Cyclosporin a 、 Cancer research 、 Multiple drug resistance 、 P-glycoprotein 、 Biology 、 Efflux 、 Mechanism of action 、 Daunorubicin transport 、 Biochemistry 、 Cytotoxicity 、 Daunorubicin
摘要: We studied the resistance of colon tumors to anticancer agents in vitro. Using daunorubicin (DN), a number cellular parameters which normally indicate acquired or multidrug (MDR), were compared for several human wild-type cell lines, i.e. HT29, SW1116 and COLO 320, murine line C-26. The sensitive/MDR ovarian cancer couple A2780/2780AD was used as reference. amount P-glycoprotein (P-gp) order A2780 ⩽ < C26 COLO320 2780AD. MDR modifiers verapamil, Cremophor EL, cyclosporin A Ro 11-2933/001 had significant effects on DN cytotoxicity, total accumulation efflux, only if P-gp present. flow-through system study mechanism transport. For first time, evidence saturation an active transport from cells is reported. discussed possible presence cooperative activity between at least two binding sites protein responsible likely be P-gp.
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