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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 TypeSingle-year Grants
Research Field Urology
Research InstitutionOITA 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
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordscisplatinum / drug resistance / prostatic cancer / 細胞内CDDP蓄積量 / DNA修復能 / シスプラチン / 耐性 / 細胞内蓄積 / グルタチオン / DNA修複
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.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Nakagawa,M et.al: "Reduction of drug accumulation in cisplatin-resistant variants of human prostatic cancer PC-3 cell line." Journal of Urology. 150. 1970-1973 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fujii,R et.al: "Active efflux system for cisplatin in cisplatin-resistant human KB cells" Japanese Jourrial of Cancer Research. 85. 426-433 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakagawa, M., Nomura, Y., Kohno, K., Ono, M., Mizoguchi, H., Ogata, J., Kuwano, M.: Journal of Urology. 150. 1970-1973 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Fujii, R., Mutoh, M., Niwa, K., Yamada, K., Aikou, T., Nakagawa, M., Kuwano, M., Akiyama, S.: Japanese Journal of Cancer Research.85. 426-433 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Masayuki Nakagawa et al: "Reduction of drug accumulation in cisplatin-resistant variants of human prostatic cancer PC-3 cell line" Journal of Urology. 150. 1970-1973 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fujii,R.et al: "Active efflux system for cisplatin in cisplatin-resistant human KB cells" Jpn.J.Cancer Res.85. 426-433 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakagawa,M et.al: "Reduction of drug accumulation in cisplatin-resistant variants of human prostatic cancer PC-3 cell line." Journal of Urology. 150. 1970-1973 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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