Antitumor effects of rosiglitazone on human breast cancer cell line MDA-MB-231 in vitro

AIM:To study the antitumor effects of peroxisome proliferator-activated receptor gamma(PPARγ)agonist rosiglitazone on human breast cancer cell line MDA-MB-231 and evaluate its underlying application value for breast cancer therapy.METHODS:MTT assay was used to observe cytostatic effects of rosiglitazone on MDA-MB-231 cells.PPARγ antagonist GW9662 was used to analyze the influence of rosiglitazone on the proliferation of MDA-MB-231 cells as well as its relationship to PPARγ.The cell cycle distribution pattern was detected by flow cytometer.Apoptotic cells were determined both by AnnexinⅤ staining and TUNEL assay.RESULTS:MTT analysis demonstrated that rosiglitazone inhibited the growth of MDA-MB-231cells in a dose-dependent manner,with IC50 being 5.2 μmol/L.PPARγ antagonist GW9662(5 μmol/L)could,at least in part,reverse the inhibitory effects of rosiglitazone on the proliferation of MDA-MB-231 cells.Cell cycle analysis showed that,with the increasing concentration of rosiglitazone treatment,the percentage of G0/G1 phase cells increased while S phase cells decreased accordingly.Apoptotic effects by rosiglitazone showed that 100 μmol/L rosiglitazone could result in cell apoptosis detected by TUNEL,and the apoptotsis rate was(18.4±3.1)%,much the same as compared to Annexin V assay by flow cytometry [(16.6±2.7)%](P0.05).CONCLUSION:Rosiglitazone treatment can inhibit the growth of MDA-MB-231 cell via PPARγ by inducing G0/G1 arrest and high dose administration of rosiglitazone can also induce the apoptosis of MDA-MB-231 cells,suggesting that PPARγ represents a putative molecular target for chemopreventive therapy and its agonist rosiglitazone might be an effective agent for the treatment of breast cancer.