Potentiation of 5-fluorouracil cytotoxicity by combining hyperthermia and dipyridamole in vitro

Evidence was obtained for the augmentation of cytotoxic effects of 5-fluorouracil (5-FU) when hyperthermia and dipyridamole (DP) were combined in vitro. Nontoxic levels of DP enhanced the combined cytotoxicity of 5-FU and heat against HeLa and B16 melanoma cells, and the 50% effective concentration of 5-FU decreased 7.3 fold for HeLa cells and 3.0 fold for B16 melanoma cells, when exposed to heat plus DP. This combined effect did not depend on intracellular increases in the concentrations of 5-FU. Thus hyperthermia together with DP seems to improve the sensitivity of tumor cells to 5-FU. As the sensitivity of colorectal cancer tissue to drugs is low, 5-FU plus hyperthermia and DP shows promise for the treatment of such patients.