Effect of Acoustic Shock Waves on Clonogenic Growth and Drug Sensitivity of Human Tumor Cells in Vitro

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Abstract
Focused acoustic shock waves were studied for their effects on human tumor cell viability, clonogenicity, and sensitivity to chemotherapeutic agents. The elastic shock waves used in this investigation were generated with the Dornier HM3-Lithotripter by underwater spark discharge with fixed electrical parameters employing a voltage of 18 kV and a capacitance of 80 nanoFarads. These waves are characterized by a fast varying compression phase, strong asymmetrical pressure and tension phases, and a maximum amplitude of roughly 108 Pascal (kg. m-1s-2). Doses as high as 2000 focused shocks showed little effect on the viability of two different cell lines. There was, however, a dose dependent inhibition of tumor cell proliferation as determined by the growth of clones in soft agarose. Each of the two cell lines showed a unique degree of colony inhibition by shock waves. It was demonstrated that shock wave effects resulted from elastic shock wave interaction with the cells and were not caused by the emission of ultraviolet light coincident with shock wave generation. Shocks were applied at a rate of 100 minute-1 in a 200 l. water bath, thereby removing the possibility for temperature changes during treatments. After treatment with shock waves it was found that tumor cells became more sensitive to growth inhibition by chemotherapeutic agents. Cisplatin, doxorubicin, and 4-hydroperoxycyclophosphamine were each more effective in blocking cell growth after the target cells had been treated with acoustic shocks. Enhanced efficacies ranged from three of 10-fold potentiation of colony inhibition. These results indicate that weak shock waves, which can be focused to a defined target region, may have utility as a cancer treatment modality either alone or in combination with cytotoxic agents.