Abstract
The human pancreatic tumour cell line PSN1/ADR, stepwise selected in 17-510 nM doxorubicin, displayed a multidrug resistance not conferred by P-glycoprotein (P-gp). Resistance to 17-51 nM doxorubicin was accompanied by overexpression of the vesicular marker lung resistance-related protein (LRP). Further selection in 170 nM doxorubicin led to the activation of multidrug resistance-associated protein (MRP) and to the development of drug accumulation/retention defects sensitive to verapamil. In addition, these defects were reversible by the vesicular traffic inhibitors brefeldin A, fluoroaluminate and nocodazole. In contrast, in human ovarian H134AD cells that are resistant to 1700 nM doxorubicin and used as P-gp-positive controls, the drug efflux was inhibited only by verapamil. The tyrosine kinase inhibitor genistein was a potent blocker of doxorubicin efflux in the PSN1/ADR cells but showed no activity in the H134 AD cells. The doxorubicin cytotoxicity in the PSN1/ADR cells was enhanced both by verapamil and brefeldin A, whereas in the parental PSN1 cells they demonstrated the opposite effects, being respectively sensitising and protecting. The P-gp-negative PSN1/ADR cells adapted to 510 nM doxorubicin retained brefeldin A-sens...Continue Reading
Citations
Mar 20, 1998·International Journal of Cancer. Journal International Du Cancer·M WartenbergH Sauer
Jan 1, 1999·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals· Christophe Minier Nancy Eufemia David Epel
Jan 19, 2019·Breast Cancer Research : BCR·Camille LehuédéCatherine Muller
Apr 23, 1999·The Journal of Biological Chemistry·D L HogueV Ling
Nov 2, 2011·Radiation Oncology·Pedro C LaraLuis Alberto Henríquez-Hernández
Feb 26, 2016·PloS One·Yanfen MaXiaoqin Wang
Mar 18, 2016·Oncology Reports·Karolina WojtowiczMaciej Zabel
Jun 17, 1998·International Journal of Cancer. Journal International Du Cancer·A B ShapiroV Ling
Jan 27, 2016·PloS One·María GetinoFernando de la Cruz
Jan 5, 2002·International Journal of Cancer. Journal International Du Cancer·Yi HuRobert E Moore
Oct 25, 2003·Oncogene·Marieke H MossinkErik A C Wiemer
Jul 17, 2004·Cancer Research·Arend van ZonErik A C Wiemer
Dec 5, 2002·Biochemistry·Kathy A Suprenant
May 1, 1997·Leukemia Research·J SedlákB Chorváth
Jun 1, 2000·Nuclear Medicine and Biology·N PerekF Dubois
Dec 18, 2001·Journal of Pharmaceutical Sciences·M D PerloffD J Greenblatt