Ｃｉｓ−ｄｉａｍｍｉｎｅ−１， １−ｃｙｃｌｏｂｕｔａｎｅ ｄｉｃａｒｂｏｘｙｌａｔｅ ｐｌａｔｉｎｕｍ （ＩＩ） を用いた温熱化学療法に関する基礎的研究

Abstract

We studied the optimal timing for the enhancement of the antitumor effects of the CDDP analogue cis-diammine-1, 1-cyclobutane dicarboxylate platinum (II)(CBDCA) combined with hyperthermia against CD-1 mice bearing Ehrlich ascites tumor (EAT) cells in vivo and the effect of hyperthermia on drug influx and efflux in vitro. The tumor doubling time was prolonged when two modalities were combined. The longest tumor doubling time was obtained by the simultaneous use of CBDCA and hyperthermia. The findings indicated that the most effective treatment was the simultaneous use of CBDCA and hyperthermia. An increase in the intratumoral platinum concentration was obtained by simultaneous treatment with CBDCA and hyperthermia.Ehrlich ascites tumor cells were used in cellular accumulation studies with a flameless atomic absorption spectrophotometer. The cells were incubated in the serum-free RD medium. After 1 hour of exposure to 40μg/ml CBDCA (final concentration), the influx at 42.5°C was approximately 2 -fold higher than control (37.0°C incubation). After 1 hour of exposure to CBDCA at 37.0°C or 42.5°C, the rate of efflux in the 5 % calf serum RD medium at 37.0°C or 42.5°C was measured after drug removal. There was a significant difference between the control group (uptake and efflux at 37.0°C) and the heated group (uptake and efflux at 42.5°C), but no significant difference between the control group and the treatment group (uptake at 42.5°C and efflux at 37.0°C). We concluded that hyperthermia increases the intracellular accumulation of CBDCA.