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 μM 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 μM RO 11–2933 (IC₁₅) or a higher dose (6 μM) 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.