Reversal Effects of Ca2+ Antagonists on Multidrug Resistance via Down-regulation of MDR1 mRNA

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In previous reports, the effects of 12 Ca2+ antagonists on a multidrug resistanttransporter, P-glycoprotein/MDR1, were evaluated in terms of those onMDR1-mediated transport of [3H]digoxin and the sensitivity of vinblastine sulfate orpaclitaxel, and they were able to be classified into 4 subgroups based on their actions,as those with transport inhibition and sensitivity recovery, those with or withouttransport inhibition but marginal sensitivity recovery, and those without both. Inthis study, our previous findings were confirmed by the resistance against doxorubicinhydrochloride and daunorubicin hydrochloride, and by the recovery of [3H] vinblastinesulfate accumulation. Furthermore, it was found that the effects of 12 Ca2+antagonists on the sensitivity recovery were also explained by the down-regulation ofMDR1 mRNA, suggesting a novel mechanism to reverse the MDR1-mediatedmultidrug resistance.
神戸大学医学部の論文
2007-12-00