Attenuating effect of PS341 for MDR1 in multidrug resistant breast cancer

2087 Background: Over-expression of P-gp has been associated with the resistance to a wide range of anti-cancer drugs. Doxorubicin and paclitaxel are substrate of this transporter system and have important role for the various human malignancies, especially in the treatment of breast cancer. Here we demonstrate that proteasome inhibitors could remarkably enhance drug sensitivities for MDR1 overexpressed multidrug resistant breast cancer and analyzed the estimated pathways involved in it Methods: Drug sensitive MCF7 and multidrug resistant MCF7/ADR (characterized by overexpression of P-gp) human breast cancer cell lines were used as an experimental model. And two proteasome inhibitors;PS341 and MG132 were used as treatment drugs. Results: PS341 and MG132, proteasome inhibitors, reduced the degree of the multidrug resistance in MCF7/ADR cells. This phenomenon was accompanied by a decrease in the IC50 value of doxorubicin and paclitaxel from 55.9±3.46 to 0.60±0.08 uM, and from 17.61±1.77 to 0.59±0.12 uM. The...