Abstract

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 cytotoxity. 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.

Author Details

Authors

• H. Schuldes¹
• J.H. Dolderer²
• C. Schoch²
• R. Bickeböller²
• B.G. Woodcock³

Departments

• ¹ Klinik für Urologie und Kinderurologie, St. Katharinenhospital Frechen,
• ² Klinik für Urologie und Kinderurologie,
• ³ Institut für Klinische Pharmakologie, Zentrum der Pharmakologie,Johann-Wolfgang-Goethe Universität, Frankfurt am Main, Germany

Address

PD Dr. H. Schuldes; Abtlg Urologie, St.-Katharinen-Hospital Frechen, Akademisches Lehrkrankenhaus der Universität Köln, Kapellenstraße 1 – 5, D-50226 Frechen, Germany

Citation