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.
Schuldes
H
H
Klinik für Urologie und Kinderurologie, St. Katharinenhospital Frechen, Germany.
Dolderer
J H
JH
Schoch
C
C
Bickeböller
R
R
Woodcock
B G
BG
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D004317:Doxorubicin; D014700:Verapamil; D002945:Cisplatin; D008727:Methotrexate