In vitro reversal of doxorubicin resistance by the tiapamil analog RO 11-2933 in human ovarian cancer cells.
The ability of RO 11-2933 to restore cellular sensitivity to doxorubicin (DX) was investigated in cultured human cancer cells with two different levels of treatment-induced resistance to DX. In the poorly resistant subline A2780-DX1, a short-term (2 h) exposure to 1 microM RO 11-2933 (IC10) completely restored DX sensitivity, whereas in the more resistant subline A2780-DX3 only partial reversal of drug resistance could be achieved by this schedule of treatment. In these cells, a long term (72 h) exposure to 1 microM RO 11-2933 (IC15) or a higher dose (6 microM) given for 2 h was required to reverse DX resistance completely. Investigation of the effects of RO 11-2933 on DX cellular accumulation and retention indicated that RO 11-2933 was able to enhance DX accumulation and reduce DX efflux within resistant cells to levels comparable to those found in sensitive cells.
Mazzoni
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Department of Pharmacology, National Institute for Cancer Research, Genova, Italy.
D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D011437:Propylamines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011437:Propylamines; D004317:Doxorubicin; C054970:Ro 11-2933