THE COMBINED EFFECTS OF HIGH-ENERGY SHOCK-WAVES AND CYTOSTATIC DRUGS OR CYTOKINES ON HUMAN BLADDER-CANCER CELLS

The effects of shock waves generated by an experimental Siemens lithot ripter in combination with cytostatic drugs or cytokines on several bl adder cancer cell lines were examined in vitro. Proliferation after tr eatment was determined with the 3-4,5-dimethylthiazol-2,5 diphenyl tet razolium bromide assay. Dose enhancement ratios were calculated for ea ch drug and each shock wave application mode in order to characterise the sensitising effect of shock wave pretreatment. The influence of th e time between shock wave and drug treatment as well as the effects of different sequences of shock wave and drug treatment or concomitant t reatment were assessed for selected combinations of cell lines and dru gs. It was found that shock wave treatment could render certain cell l ines more susceptible to subsequent cis-platinum, mitomycin C or actin omycin D incubation. Cell lines sensitive to tumour necrosis factor a or interferon a were further sensitised to these cytokines by shock wa ve pretreatment. The enhanced sensitivity to cis-platinum and actinomy cin D decreased rapidly during the first hours after shock wave treatm ent. The antiproliferative effect was most pronounced after concomitan t shock wave and drug treatment. The sensitisation to interferon a dim inishes more slowly after shock wave exposure. From the results presen ted in this study it is concluded that transient shock wave-induced pe rmeabilisation of cell membrane not only enhances drug efficiency, but also causes damage to cell organelles and alterations in cellular met abolism