Effect of Hyperthermia on Cis-Diamminedi Chloroplatinum(II) (Rhodamine 123)2[Tetrachloroplatinum(II)] in a Human Squamous Cell Carcinoma Line and a M-Diammine-Dichloroplatinum(II)-Resistant Subline

Terence S. Herman, Beverly A. Teicher, Kathleen N.S. Cathcart, Mark E. Kaufmann, Jonathan B. Lee, Mi Hyon Lee

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69 Scopus citations

Abstract

The effect of concomitant hyperthermia on the cytotoxicities of cis-diamminedi chloroplatinum(II) (CDDP), a newly synthesized drug, Pt(Rh-123)2, and its chemical components, K2PtCl4 and rhodamine 123, was examined in vitro in a squamous cell tumor line of human origin (SCC-25) and in a CDDP-resistant subline (SCC-25/CP). No difference in the cytotoxicity of hyperthermia alone was observed between these cell lines. The dose-dependent cytotoxicities of 1-h exposures to CDDP and Pt(Rh-123)2 were markedly increased at 42°C and 43°C in comparison to 37°C, and this effect was of the same magnitude in both cell lines (enhancements of approximately 1.5 logs at 42°C and 2.5 logs at 43°C for CDDP and 1.5 logs at 42°C and >3 logs at 43°C for Pt(Rh-123)2). The use of hyperthermia with CDDP, however, did not lower survivals in the SCC-25/CP cells even to the levels seen in the parent line at 37°C. The cytotoxicities of K2PtCl4 and rhodamine 123 were essentially the same in the CDDP-sensitive and -resistant cells at all temperatures tested. The magnitude of the temperature effect was significantly greater for Pt(Rh-123)2 than for its chemical components. No significant effect on CDDP or Pt(Rh-123)2 accumulation was observed at 42, 43, 44 or 45°C in either cell line. DNA lesions, measured by alkaline elution, were significantly enhanced for CDDP in the SCC-25 cells at 42°C. These results suggest that treatment with hyperthermia and either CDDP or Pt(Rh-123)2 should result in supraadditive anti-tumor effects, although the efficacy of CDDP plus hyperthermia will be significantly less once resistance to CDDP has developed. Since resistance to CDDP does not imply cross-resistance to Pt(Rh-123)2, and since the effect of hyperthermia is somewhat greater for Pt(Rh-123)2 than for CDDP at 43°C, Pt(Rh-123)2 may be more selectively toxic to tumor cells when used with local hyperthermia versus normal cells outside the treated area, especially if resistance to CDDP has already developed.

Original languageEnglish (US)
Pages (from-to)5101-5105
Number of pages5
JournalCancer Research
Volume48
Issue number18
StatePublished - Sep 1988
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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