Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 355-363 |
| Number of pages | 9 |
| Journal | Kobe Journal of Medical Sciences |
| Volume | 53 |
| Issue number | 6 |
| Publication status | Published - 2007 |
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Keywords
- Ca antagonist
- Down-regulation
- MDR1/P-glycoprotein
- mRNA expression
- Multidrug resistance
ASJC Scopus subject areas
- Medicine(all)
Cite this
Reversal effects of Ca2+ antagonists on multidrug resistance via down-regulation of MDR1 mRNA. / Komoto, Chiho; Nakamura, Tsutomu; Yamamori, Motohiro; Ohmoto, Nobuko; Kobayashi, Hironao; Kuwahara, Akiko; Nishiguchi, Kohshi; Takara, Kohji; Tanigawara, Yusuke; Okamura, Noboru; Okumura, Katsuhiko; Sakaeda, Toshiyuki.
In: Kobe Journal of Medical Sciences, Vol. 53, No. 6, 2007, p. 355-363.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reversal effects of Ca2+ antagonists on multidrug resistance via down-regulation of MDR1 mRNA
AU - Komoto, Chiho
AU - Nakamura, Tsutomu
AU - Yamamori, Motohiro
AU - Ohmoto, Nobuko
AU - Kobayashi, Hironao
AU - Kuwahara, Akiko
AU - Nishiguchi, Kohshi
AU - Takara, Kohji
AU - Tanigawara, Yusuke
AU - Okamura, Noboru
AU - Okumura, Katsuhiko
AU - Sakaeda, Toshiyuki
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
KW - Ca antagonist
KW - Down-regulation
KW - MDR1/P-glycoprotein
KW - mRNA expression
KW - Multidrug resistance
UR - http://www.scopus.com/inward/record.url?scp=45749149886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45749149886&partnerID=8YFLogxK
M3 - Article
C2 - 18762730
AN - SCOPUS:45749149886
VL - 53
SP - 355
EP - 363
JO - Kobe Journal of Medical Sciences
JF - Kobe Journal of Medical Sciences
SN - 0023-2513
IS - 6
ER -