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Analysis of the cytotoxic interaction between cisplatin and hyperthermia in a human ovarian carcinoma cell line

  • Original Articles
  • Cisplatin, HSP-60, Hyperthermia, Cytotoxicity
  • Published:
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Abstract

Expression of the heat-shock protein HSP-60 is associated with poor survival in patients with ovarian carcinoma. We examined both the nature of the interaction between hyperthermia and cisplatin (DDP) using the human ovarian carcinoma cell line 2008 and the effect on this interaction of the induction of the heat-shock response. The nature of the interaction was assessed using medianeffect analysis. Despite the observation that 45°C hyperthermia increased the intracellular uptake of the DDP analog [3H]-cis-dichloro(ethylenediamine)platinum(II)(DEP) during a 1-h exposure by 155%±5% (P=0.02), median-effect analysis indicated only cytotoxic additivity (combination index at the level of 50% cell kill, 0.96±0.25). When cells were first exposed to hyperthermia for various periods and then allowed to incubate at 37° C for 4 h to allow induction of the heat-shock genes before being treated with DDP for 1 h, there was a very small degree of antagonism between hyperthermia and DDP (combination index at 50% cell kill, 1.11±0.04). Our results indicate that DDP and hyperthermia interact only in an additive manner against this human ovarian carcinoma cell line and that the induction of heat-shock proteins by hyperthermia does not significantly antagonize the activity of DDP.

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Abbreviations

CI:

combination index

DDP:

cisplatin

DEP:

cis-dichloro(ethylenediamine)platinum(II)

IC50 :

concentration or time producing 50% inhibition of colony formation

PBS:

phosphate-buffered saline

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, 105, Tokyo, Japan

    Eizo Kimura

  2. Department of Medicine, University of California, San Diego, 92093-0812, La Jolla, CA, USA

    Stephen B. Howell

  3. Cancer Center, University of California, San Diego, 92093-0812, La Jolla, CA, USA

    Stephen B. Howell

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  1. Eizo Kimura
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  2. Stephen B. Howell
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Additional information

This work was supported by grant CH-377 from the American Cancer Society and grant 100-R041 from Bristol-Myers Squibb. This work was conducted in part by the Clayton Foundation for Research — California Division. Dr. Howell is a Clayton Foundation investigator

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Kimura, E., Howell, S.B. Analysis of the cytotoxic interaction between cisplatin and hyperthermia in a human ovarian carcinoma cell line. Cancer Chemother. Pharmacol. 32, 419–424 (1993). https://doi.org/10.1007/BF00685884

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  • DOI: https://doi.org/10.1007/BF00685884

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