Potentiation of the chemotherapeutic effect of methotrexate by hyperthermia in experimental animal tumor model

ABSTRACT

Evidence was obtained for the augmentation of cytotoxic effect of methotrexate [MTX] when combined with hyperthermia [HPT] in vivo. Results showed that Ehrlich tumor bearing mice injected i.p. with a single dose of MTX [1 mg/kg] 1 hour prior to local treatment with HPT [43C for 30 minutes] produced 2-fold enhancement of the tumor growth delay induced by MTX alone. Treatment of HPT alone for 3 times every other day produced 41.5% tumor regression, however, combined treatment of MTX and HPT produced 76.3% decrease in tumor volume compared to their volume before the treatment. The molecular mechanisms responsible for this potentiation were investigated by assaying tumor tissue contents of DNA, RNA and protein, and their rate of synthesis. Total lipid, cholesterol as well as activities of acid phosphatase and acid ribonuclease were also determined