The purpose of this study was to determine whether agonists and antagonists of α-adrenoceptors that affect calcium fluxes and protein kinase C signal transduction after the chemosensitivity of cancer cells that exhibit multidrug resistance (MDR). The effects of nine α-adrenoceptor agonists or antagonists on the in vitro chemosensitivity of the UV-2237 murine fibrosarcoma and its doxorubicin-selected MDR variants (UV-2237-R1 and UV-2237-R10) were examined. Noncytotoxic concentrations of the α-adrenoceptor antagonist furobenzazepine enhanced the antitumor activity of doxorubicin, actinomycin D, vinblastine and vincristine, but not 5-fluorouracil. Similar effects of furobenzazepine were also observed in recently established doxorubicin-resistant MDR variants of the CT-26 murine colon carcinoma. The chemosensitizing effect of furobenzazepine was associated with an increase in intracellular accumulation of anticancer drugs. Furobenzazepine did not compete with [3H]azidopine for photoaffinity labeling of P-glycoprotein, but it did produce a transient 30% reduction of P-glycoprotein in the MDR cells. These data indicate that furobenzazepine can reverse a P-glycoprotein-mediated experimental MDR phenotype.
|Original language||English (US)|
|Number of pages||10|
|Journal||International journal of oncology|
|State||Published - Jan 1 1994|
ASJC Scopus subject areas
- Cancer Research