Cytostatic sensitivity and MDR in bladder carcinoma cells: implications for tumor therapy.

The clinical success generally seen in chemotherapy of advanced bladder carcinoma is far from optimal. The mechanism of resistance development is unclear and the expression of P-170 glycoprotein is generally low. The aim of this study, carried out in vitro in sensitive and cisplatin-resistant cell lines, was to examine sensitivity modulation using R-verapamil and cell membrane perturbing agents. Cell growth rates and changes in the order of the cell membrane, determined using electron-paramagnetic resonance spectrometry, were recorded. R-verapamil increased the toxic effect of doxorubicin in the cisplatin-resistant cell line which showed the highest membrane order. Linolenic acid had a similar effect and also increased sensitivity to cisplatin and methotrexate. Bile salts (tauro-cheno-deoxycholate,TCDC, and tauro-urso-deoxycholate TUDC), had little effect on cytotoxicity. These results indicate that R-verapamil and linolenic acid can act as sensitivity modulators in bladder carcinoma cells and that the action of these agents may involve membrane fluidity changes, a phenomenon noted previously in regard to sensitivity modulation in chinese hamster ovary cell lines.