Reversal by a dihydropyridine derivative of non-P-glycoprotein-mediated multidrug resistance in etoposide-resistant human prostatic cancer cell line.

Abstract

PURPOSE:

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.

MATERIALS AND 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.

• Authors: Y Tasaki, M Nakagawa, J Ogata, A Kiue, H Tanimura, M Kuwano, Y Nomura
• Journal: The Journal of urology (J Urol) Vol. 154 Issue 3 Pg. 1210-6 (Sep 1995) ISSN: 0022-5347 [Print] United States
• PMID: 7637090 (Publication Type: Journal Article)

Chemical References

• Dihydropyridines
• NIK 250
• RNA, Messenger
• Sulfur Compounds
• Etoposide

Topics

• Cell Line
• Dihydropyridines (pharmacology)
• Drug Resistance, Multiple (genetics)
• Etoposide (pharmacology)
• Humans
• Male
• Prostatic Neoplasms
• RNA, Messenger (analysis)
• Sulfur Compounds
• Tumor Cells, Cultured
• Tumor Stem Cell Assay