AUGMENTATIVE EFFECTS OF INTRACELLULAR CHEMOTHERAPY PENETRATION COMBINED WITH HYPERTHERMIA IN HUMAN OVARIAN-CANCER CELLS LINES

A significant proportion of ovarian cancer patients do not achieve a complete response to chemotherapy, due mainly to the evolution of clones resistant to cytotoxic drugs. Exploring possibilities to overcome this resistance constitutes a challenge in the study of ovarian cancer experimental therapy. In the present study, we tested the effect of hyperthermia (40 and 43 degrees C) in combination with adriamycin on three human epithelial ovarian cell lines: OC-109, OC-238, and OC-7-NU. The first was derived from the mucinous and the other two from serous cystadenocarcinomas, and all proved to be tumorigenic in nude mice. FACS analysis showed a pronounced increase in intracellular adriamycin accumulation in the presence of hyperthermia. A significant effect (P < 0.0005) observed at 40 degrees C was even more pronounced at 43 degrees C with the three cell lines. High percentages of cells (up to 70%) shifted into higher fluorescence intensities. The lines differed in their sensitivity to the hyperthermia-induced increase in adriamycin accumulation. Under mild conditions, the OC-109 line was more sensitive than the OC-238 and the OC-7-NU lines. Quantitative determination of intraneoplastic adriamycin by spectrofluorometry also showed a hyperthermia-related increase in intracellular adriamycin (P < 0.005). Our results may indicate that supranormal temperature might serve as an alternative chemosensitizer which lacks the deleterious side effects of other chemosensitizing options. (C) 1994 Academic Press, Inc.