In vitro reversal of doxorubicin resistance by the tiapamil analog RO 11-2933 in human ovarian cancer cells.

Abstract

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.

• Authors: A Mazzoni
• Journal: Tumori (Tumori) Vol. 76 Issue 1 Pg. 69-72 (Feb 28 1990) ISSN: 0300-8916 [Print] United States
• PMID: 2321277 (Publication Type: Journal Article)

Chemical References

• Propylamines
• Doxorubicin
• Ro 11-2933

Topics

• Doxorubicin (pharmacokinetics, pharmacology)
• Drug Resistance
• Drug Synergism
• Female
• Humans
• Ovarian Neoplasms (pathology)
• Propylamines (pharmacology)
• Tumor Cells, Cultured (drug effects)