Increased chemocytotoxicity to colon cancer cells by shock wave-induced cavitation.

Abstract

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. 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 [3H]deoxyuridine ([3H]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. 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 [3H]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 [3H]dUdR incorporation was reduced by up to 1 log, and TS inhibition was increased after cavitation as compared with FUra alone. RNA incorporation of [14C]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. 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.