Growth Inhibiton of Human Breast Cancer Cell Line MDA-MB-231 by Rosiglitazone through Activation of PPAR γ

Tao ZHANG, Qian ZHANG, Daixiong CHEN, Jianxin JIANG, Qixin ZHOU

Abstract


OBJECTIVE    To investigate the anti-proliferative effect of rosiglitazone and its relationship to peroxisome proliferator activated 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-MB231 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 PPAR γ antagonist GW9662 to investigate the eff ect 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 μ mol/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 G1phase with increasing concentrations of rosiglitazone. Detectable signs of apoptotic cell death caused by rosiglitazone occurred at a concentration of 100 μ mol/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.

Keywords


peroxisome proliferator-activated receptor γ (PPARγ ), rosiglitazone,MDA-MB-231 cells, antiproliferative effects, apoptosis KOLLA anti-proliferative.

Full Text: PDF

Refbacks

  • There are currently no refbacks.



OUR FRIENDS