TY - JOUR
T1 - 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
AU - Herman, Terence S.
AU - Teicher, Beverly A.
AU - Cathcart, Kathleen N.S.
AU - Kaufmann, Mark E.
AU - Lee, Jonathan B.
AU - Lee, Mi Hyon
PY - 1988/9
Y1 - 1988/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0023680689&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023680689&partnerID=8YFLogxK
M3 - Article
C2 - 3409235
AN - SCOPUS:0023680689
SN - 0008-5472
VL - 48
SP - 5101
EP - 5105
JO - Cancer Research
JF - Cancer Research
IS - 18
ER -