Sensitization of breast cancer cells to taxol by inhibition of taxol resistance gene 1.

The purpose of this study was to determine the role of taxol resistance gene 1 (TXR1) in a taxol-resistant breast cancer cell line. Expression levels of TXR1 and thrombospondin-1 (TSP1) were detected by RT-PCR and Western blot analysis. In MCF-7 cells transfected with TXR1 plasmids, the expression of a number of drug resistance genes was monitored, as well as cell proliferation. MCF-7 cells were also transiently transfected with a chemically synthesized small interfering RNA (siRNA) targeting TXR1. Taxol concentrations varying from 0.6 to 6 μg/ml were shown to inhibit the proliferation of MCF-7 cells in a time- and dose-dependent manner by arresting cells in the G2/M phase. Additionally, 0.06 μg/ml taxol was used to establish a taxol-resistant MCF-7 cell line, MCF-7/T. When TXR1 was exogenously expressed, a taxol-resistant phenotype was further induced and the expression levels of BCRP, GSTP1 and MVP increased. Transient transfection of TXR1-targeting siRNAs was shown to restore the chemosensitivity of MCF-7 cells. These results suggest that an increased expression of TXR1 is a novel mechanism for reversing the taxol resistance of breast cancer cells.