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1997 Fiscal Year Final Research Report Summary

The relation of the anti-cancer drug resistance and heat shock protein 60 expression

Research Project

Project/Area Number 07671826
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionJikei University School of Medicine

Principal Investigator

KIMURA Eizo  Jikei University school of Medicine, Department Obstetrics and Gynecology, Instructor, 医学部, 講師 (70161552)

Project Period (FY) 1995 – 1997
Keywordsheat shock / hyperthermia / cancer / drug resistance / survival / anti-cancer drug
Research Abstract

The expression of the 60-kDa heat-shock protein (HSP60) varies markedly among pateints with ovarian carcinoma, and high-level expression predicts poor survival in such patients treated with cisplatin (DDP)-containing chemotherapy programs. I investigated the expression of HSP60 in human ovarian carcinoma 2008 cells and an 11-fold DDP-resistant subline 2008/C13<@D1**@>D15.25. Heating for 2 h at 44゚C produced a 2.7(]SY.+-。[)0.16-fold increase (mean (]SY.+-。[)SD) that was maximal at 4 h after the start of heat exposure. Exposure to an IC50 concentration of DDP for 1 h induced a 1.8(]SY.+-。[)0.03-fold increase in hsp60 expression. The opposite was true for cadmimum and zinc, both of which induced increases in metallothionein IIA but not in the hsp60 message. 2008/C13<@D1**@>D15.25 cells cnstitutively overexpressed hsp60 mRNA by 1.7(]SY.+-。[)0.16 orders of magmitude and contained a 3.8(]SY.+-。[)0.45-fold higher level of HSP60as detected by immunocytochemical satining. 2008/C13<@D1**@>D15.25 cells showed 1.2-fold cross-resistance to thermal killing. Expression of hsp60 was markedly reducedin 2008 xenografts as compared with 2008 cells growing in-vitro ; however, neither serum starvation nor refeeding altered the message level. Exposure to a variety of growth factor and drug treatments known to alter the DDP sensitivity of2008 cells, including epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, buthionine sulfoximine, ouabain, and forskolin, did not alter hsp60 expression. These results suggest a role for HSP60 in mediating resistance to both DDP and hyperthermia but indicate that the hsp60 mRNA levels are not regulated by the factors listed above.

  • Research Products

    (1 results)

All Other

All Publications (1 results)

  • [Publications] Yoshihiro Kikuchi(Ed.): "The Mechanism of Cisplatin Resistance and its Circumvention" Nova Science Publishers,Inc. (in print), (1998)

    • Description
      「研究成果報告書概要(和文)」より

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Published: 1999-03-16  

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