Effects of pre-heating on cis-diamminedichloroplatinum(II)-hyperthermia-induced tumour growth depression of transplantable human oesophageal cancer to nude mice

Abstract

The effects of the combination of cis-diamminedichloroplatinum(II) (CCDP) and hyperthermia on tumour growth were examined using transplantable human oesophageal cancer (ESO-2), having a histological type of moderately differentiated squamous cell carcinoma, in nude mice. Eighteen days after the inoculation of the tumour fragment into the subcutaneous tissue of the right hind foot, the treatment of CDDP and/or hyperthermia was performed and the antitumour effect was evaluated 21 days after the treatment. The combination of 4 mg/kg of CDDP and 43˚C heating for 30 min effectively depressed tumour growth in comparison with the individual treatment. The mean relative tumour weight of the combination group at 3 weeks after the treatment was 15% of that of the control group without treatment. On the other hand, pre-heating at 42˚C for 30 min did not influence the inhibition of tumour growth by CDDP alone or the concentration of CDDP in tumour. When pre-heating at 42˚C for 30 min was performed at 6 or 12 h prior to the combined treatments of 2 mg/kg of CDDP and 43˚C hyperthermia for 30 min, however, tumour growth depression by CDDP-hyperthermia was diminished. When pre-heating was performed 4 days prior to CDDP-hyperthermia, however, tumour growth depression occurred. These results showed that thermotolerance of tumour cells induced by pre-heating diminished hyperthermic potentiation for cytotoxicity of CDDP, though the thermotolerance did not affect the cytotoxicity of CDDP.

Key Words:

• Hyperthermia
• CDDP
• oesophageal cancer
• nude mice
• thermotolerance