ENHANCEMENT OF HYPERTHERMIC TOXICITY BY LONIDAMINE IN THE DUNNING R3327G RAT PROSTATIC ADENOCARCINOMA

Hyperthermia alone or with radiation is used therapeutically for localized solid tumors. Clinical experience shows that sustained tumor temperature exceeding 45 degrees C damages normal tissue. Any agent that enhances the effects of hyperthermia at or below this temperature may have clinical relevance. Lonidamine and hyperthermia were tested on the Dunning R3327G rat prostatic adenocarcinoma. Using colony-formation assays, cytotoxic effects of each agent alone and in combination were quantified. Lonidamine to 100 mu g/ml was not significantly toxic, but in combination, it enhanced cytotoxicity. Survival patterns after fractionated hyperthermia revealed a rapid development and decay of thermotolerance. Measurement of cell-cycle progression following a single dose of hyperthermia revealed a reduction of S-phase cells, and subsequent accumulation in G(1) over 24 hours. Combination treatment of tumor-bearing rats significantly reduced tumor growth rate when compared with individual agents. These results suggest a potential use of lonidamine in hyperthermic therapy of prostate tumors. (C) 1994 Wiley-Liss, Inc.