[Troglitazone sensitizes effect of epirubicin on breast cancer cells].
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.
Sun
Jing-Xia
JX
Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 210029, P. R. China.
Meng
Zhuo-Xian
ZX
Lv
Jing-Huan
JH
Sun
Yu-Jie
YJ
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D015536:Down-Regulation; D004357:Drug Synergism; D015251:Epirubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D002839:Chromans; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D045162:Thiazolidinediones; D015251:Epirubicin; D000077288:Troglitazone