REDUCTION OF DRUG ACCUMULATION IN CISPLATIN-RESISTANT VARIANTS OF HUMAN PROSTATIC-CANCER PC-3 CELL-LINE

被引：33
|
作者：
NAKAGAWA, M [1 ]
NOMURA, Y [1 ]
KOHNO, K [1 ]
ONO, M [1 ]
MIZOGUCHI, H [1 ]
OGATA, J [1 ]
KUWANO, M [1 ]
机构：
[1] OITA MED UNIV,DEPT BIOCHEM,OITA,JAPAN
来源：
JOURNAL OF UROLOGY | 1993年 / 150卷 / 06期
关键词：
CISPLATIN; DRUG RESISTANCE; PROSTATIC NEOPLASMS;
D O I：
10.1016/S0022-5347(17)35948-7
中图分类号：
R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];
学科分类号：
1002 ; 100201 ;
摘要：
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 mug./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.
引用
收藏
页码：1970 / 1973
页数：4
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