Reversal effects of Ca2+ antagonists on multidrug resistance via down-regulation of MDR1 mRNA.
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 Ca2+ 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.
Komoto
Chiho
C
Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe 650-0017, Japan.
Nakamura
Tsutomu
T
Yamamori
Motohiro
M
Ohmoto
Nobuko
N
Kobayashi
Hironao
H
Kuwahara
Akiko
A
Nishiguchi
Kohshi
K
Takara
Kohji
K
Tanigawara
Yusuke
Y
Okamura
Noboru
N
Okumura
Katsuhiko
K
Sakaeda
Toshiyuki
T