Reversal by a dihydropyridine derivative of non-P-glycoprotein-mediated multidrug resistance in etoposide-resistant human prostatic cancer cell line.
OBJECTIVE
We have isolated etoposide-resistant prostatic cancer cell lines, P/VP10 and P/VP20, to investigate the multidrug resistance (MDR) mechanism and to find MDR reversal agents.


METHODS
We examined expression of MDR-related genes and screened reversal agents of MDR in P/VP20 cells.


RESULTS
These cells demonstrated a non-P-glycoprotein (P-gp)-mediated MDR phenotype with overexpression of MDR-associated protein (MRP) mRNA due to MRP DNA amplification. A 1,4-dihydropyridine derivative, bis(4-pyridylmethyl)4-[2-(3-methyl-5,6- dihydro-1,4-dithiinyl)]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicar boxylate (NIK250), was found to overcome MDR in P/VP20 cells.


CONCLUSIONS
NIK250 might be useful in reversing MDR, which often develops during chemotherapy of advanced or hormone-resistant prostatic cancer.
Tasaki
Y
Y
Department of Urology and Surgery, Oita Medical University, Japan.
Nakagawa
M
M
Ogata
J
J
Kiue
A
A
Tanimura
H
H
Kuwano
M
M
Nomura
Y
Y
D002460:Cell Line; D004095:Dihydropyridines / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000032:analysis; D013457:Sulfur Compounds; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D004095:Dihydropyridines; C095013:NIK 250; D012333:RNA, Messenger; D013457:Sulfur Compounds; D005047:Etoposide