Background & objective: Peroxisome proliferator-activated receptor gamma (PPARgamma) is known to be highly expressed in breast cancer tissues. Thiazolidinediones (TZD), the specific ligands for PPARgamma, can inhibit cell proliferation and induce apoptosis. This study was to investigate the possibility of using troglitazone, one of TZD, as the sensitizer of epirubicin in the treatment of estrogen receptor (ER) negative breast cancer.
Methods: MTT assay and flow cytometry were used to examine the cell proliferation and apoptosis in two ER negative breast cancer cell line MDA-MB-435S and MDA-MB-231. Cells were treated with either troglitazone or epirubicin alone or co-treated with troglitazone and epirubicin. Western blot analysis was used to assess the expression level of Bcl-2. The migration potential of cells with different treatments was analyzed by the wound healing assay.
Results: The effect of epirubicin on inhibiting cell proliferation of breast cancer cells was enhanced by co-treatment with troglitazone in the range of 4 micromol/L to 24 micromol/L. The 50% inhibitory concentration (IC(50)) of epirubicin was reduced to 60% when combined with troglitazone compared to the treatment with epirubicin only. Treatment of cells with troglitazone or epirubicin alone could not induce significant apoptosis. However, the apoptotic indexes of MDA-MB-435S and MDA-MB-231 cells co-treated with troglitazone and epirubicin were (5.48+/-0.45)% and (10.08+/-1.89)%, respectively. Co-treatment with troglitazone and epirubicin further downregulated the expression level of Bcl-2 and inhibited cell migration simultaneously.
Conclusions: Troglitazone could not only augment the effect of epirubicin on inhibiting cell proliferation and inducing apoptosis, but also suppress the migration of breast cancer cells. Troglitazone may sensitize the effect of epirubicin on breast cancer cells.