In previous reports, the effects of 12 Ca2+ antagonists on a multidrug resistant transporter, P-glycoprotein/MDR1, were evaluated in terms of those on MDR1-mediated transport of [3H]digoxin and the sensitivity of vinblastine sulfate or paclitaxel, 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 without transport inhibition but marginal sensitivity recovery, and those without both. In this study, our previous findings were confirmed by the resistance against doxorubicin hydrochloride and daunorubicin hydrochloride, and by the recovery of [3H] vinblastine sulfate accumulation. Furthermore, it was found that the effects of 12 Ca 2+ antagonists on the sensitivity recovery were also explained by the down-regulation of MDR1 mRNA, suggesting a novel mechanism to reverse the MDR1-mediated multidrug resistance.
|Number of pages||9|
|Journal||Kobe Journal of Medical Sciences|
|Publication status||Published - 2007 Jan 1|
- Multidrug resistance
- mRNA expression
ASJC Scopus subject areas