Abstract
The development of tumor cell drug resistance is a major obstacle which often leads to the failure of cancer chemotherapy. We studied the cytotoxic and pharmacological properties of 40°C hyperthermia and CDDP in CDDP-sensitive (IMC-3) and CDDP-resistant (IMC-3-DDP) human maxillary carcinoma cells. IMC-3 and IMC-3-DDP cells did not differ in heat sensitivity at 40°C. Heating at 40°C potentiated CDDP cytotoxicity in both IMC-3 and IMC-3-DDP cells with thermal chemoenhancement ratios (C. E. R.) of 1.48 and 1.94, respectively. The intracellular CDDP uptake level of IMC-3-DDP at 37°C was significantly reduced to about 60% compared with IMC-3 cells. At 40°C, however, hyperthermia increased platinum accumulation by factors of 1.4 and 1.8 in IMC-3 and IMC-3-DDP cells, respectively. CDDP sensitivity was hyperthermically chemopotentiated in CDDP-resistant variants rather than in the control clones.
Thus, clinical cancer chemotherapy with CDDP may be improved by an appropriate combination with hyperthermia even at 40°C.
