1994 Fiscal Year Final Research Report Summary

STUDIES ON MECHANISMS OF CISPLATINUM-RESISTANCE IN URINARY TUMORS AND DRUG SCREENING FOR REVERSAL OF THE RESISTANCE.

Research Project

Project/Area Number	05671326
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Urology
Research Institution	OITA MEDICAL UNIVERSITY
Principal Investigator	NAKAGAWA Masayuki Oita Medical University, Department of Urology, Assistant Professor, 医学部, 講師 (90164144)
Project Period (FY)	1993 – 1994
Keywords	cisplatinum / drug resistance / prostatic cancer
Research Abstract	We have isolated cisplatinum (CDDP) -resistant cell lines, P/CDP4 and P/CDP5, from human PC-3 prostatic cancer cells after a stepwise exposure to CDDP to elucidate mechanisms of cisplatinum-resistance in urinary tumors.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 PC-3, respectively, when PC-3 and its CDDP-resistant counterparts were incubated with 5 and 10 mug/ml of CDDP for 24 hrs.These data suggest that decreased drug accumulation is involved in the development of CDDP-resistance in the PC-3 cell line.