Valspodar restores paclitaxel-induced apoptosis in the adriamycin-resistant human breast cancer cell line MCF7/adr*

Paclitaxel (taxol™) is one of the most effective chemotherapy agents for the treatment of metastatic breast cancer. It is one of only three agents that kill breast cancer cells by inducing both necrosis and apoptosis. Multidrug resistance (MDR) is a clinical phenomenon and a major impediment to effective clinical treatment with taxol. Valspodar is a second-generation cyclosporin derivative that has been shown to reverse MDR in cells by blocking the function of the membrane bound drug transporter P-glycoprotein (P-GP). P-glycoprotein enables tumour cells to efflux a wide variety of chemotherapy agents out of the cell. Whether valspodar can restore taxol-induced apoptosis in breast cancer cells resistant to another highly effective drug used in the treatment of breast cancer, doxorubicin (adriamycin) has not been established. This study aimed to examine this question. (Abstract shortened by UMI.)...