Reduction of drug accumulation in cisplatin-resistant variants of human prostatic cancer PC-3 cell line.
We have isolated cis-diamminedichloroplatinum (II) (CDDP)-resistant variants, P/CDP4 and P/CDP5, from human prostatic cancer PC-3 cells after a stepwise exposure to CDDP. P/CDP4 and P/CDP5 showed 11-fold and 23-fold higher resistance to CDDP than did PC-3. P/CDP5 was cross-resistant to carboplatin, mitomycin C, etoposide, m-AMSA, bleomycin and UV irradiation. Alkaline elution of DNA showed an increased amount of DNA interstrand cross-links in PC-3 but not in P/CDP5 when PC-3 and P/CDP5 were cultured with CDDP. Flameless atomic absorption spectrophotometry revealed that intracellular accumulation of CDDP in P/CDP4 and P/CDP5 was decreased to 18 to 34% and 9 to 18% of that of PC-3, respectively, when PC-3 and its CDDP-resistant counterparts were incubated with 5 and 10 micrograms./ml. of CDDP for 24 hours. These data suggest that decreased drug accumulation is involved in the development of CDDP-resistance in the PC-3 cell line.
Nakagawa
M
M
Department of Urology, Oita Medical University, Japan.
Nomura
Y
Y
Kohno
K
K
Ono
M
M
Mizoguchi
H
H
Ogata
J
J
Kuwano
M
M
D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D004273:DNA, Neoplasm; D002945:Cisplatin