RT Journal Article
SR Electronic
T1 Growth Inhibiton of Human Breast Cancer Cell Line MDA-MB-231 by Rosiglitazone through Activation of PPARγ
JF Chinese Journal of Clinical Oncology
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 407
OP 412
DO 10.1007/s11805-008-0407-6
VO 5
IS 6
A1 Tao Zhang
A1 Qian Zhang
A1 Daixiong Chen
A1 Jianxin Jiang
A1 Qixin Zhou
YR 2008
UL http://www.cancerbiomed.org/content/5/6/407.abstract
AB OBJECTIVE To investigate the anti-proliferative effect of rosiglitazone and its relationship to peroxisome proliferatoractivated receptor γ (PPARγ) in human breast cancer cell line MDA-MB-231 and evaluate the potential application value of rosiglitazone for breast cancer therapy.METHODS The cytostatic effect of rosiglitazone on MDA-MB-231 cells was measured by the MTT assay. Cell-cycle kinetics was assessed by flow cytometry. Apoptotic cells were determined by the TUNEL assay. MDA-MB-231 cells were treated with rosiglitazone or in combination with the PPARγ antagonist GW9662 to investigate the effect of rosiglitazone on cell proliferation and its relationship to PPARγ.RESULTS The results showed that rosiglitazone could inhibit growth of MDA-MB-231 cells in a dose- and time-dependent manner with an IC50 value of 5.2 μmol/L at 24 h after the drug was added into the culture. Cell cycle analysis showed that the percentage of G0/G1 phase cells increased, S phase cells decreased, and cells were arrested in G1 phase with increasing concentrations of rosiglitazone. Detectable signs of apoptotic cell death caused by rosiglitazone occurred at a concentration of 100 μmol/L and the apoptotic rate was (18 ± 3)%. PPARγ selective antagonist GW9662 could partially reverse the inhibitory effect of rosiglitazone on proliferation of MDA-MB-231 cells.CONCLUSION It was concluded that rosiglitazone can inhibit growth of MDA-MB-231 cells via PPARγ activation and a high concentration of rosiglitazone can also induce MDA-MB-231 cell apoptosis. These results suggest that PPARγ represents a putative molecular target for chemopreventive therapy and rosiglitazone may be effective in the treatment of breast cancer.