INCREASED CHEMOCYTOTOXICITY TO COLON-CANCER CELLS BY SHOCK WAVE-INDUCED CAVITATION

Background/Aims: Cavitation has been shown to hinder colon cancer cell proliferation in vitro. This study aimed at investigating the interest of combining cavitation and cytotoxic drugs in vitro. Methods: HT-29 cells were exposed in suspension to cavitation (shock waves plus bubbles) before 5-fluorouracil (FUra) administration. Cytotoxicity was studied by means of clonogenic survival, cell proliferation by [H-3]deoxyuridine ([H-3] dUdR) incorporation, and influence of the treatments on the cell cycle by cytofluorimetry; the effects of cavitation on RNA incorporation of FUra, cell permeability, and activity of thymidilate synthetase (TS) were also studied. Results: A preliminary exposure to cavitation (as compared with FUra alone) induced decreased colony formation (by up to 2 log in certain conditions) and colony size. Cavitation alone induced increased incorporation of [H-3]dUdR during 48 hours and stimulated TS activity, but in the presence of FUra, the concentration of the drug that causes 50% inhibition of control cell growth for [H-3]dUdR incorporation was reduced by up to 1 log, and TS inhibition was increased after cavitation as compared with FUra alone. RNA incorporation of [C-14]FUra was increased by cavitation, as a consequence of altered cell permeability rather than a direct RNA effect. Seventy-two hours after treatment, cavitation plus FUra decreased by more than 50% the S-phase fraction and also inhibited mitosis. Conclusions: Submitting HT-29 cells to cavitation before treatment by FUra significantly increases the effects of the drug. The action of both agents appears to be partially synergistic with a cycle specificity.