Osthole inhibits the proliferation of breast cancer MCF-7 cells via activating peroxisome proliferator-activated receptor γ / 肿瘤研究与临床

ABSTRACT

Objective To investigate the effect of osthole on the proliferation and apoptosis of breast cancer cell line MCF-7 and its potential mechanisms.Methods Breast cancer cell line MCF-7 was treated by osthole 0,25,50,100,150 and 200 μmol/L respectively.MTT method was used to detect cell survival rate.HE staining was used to observe morphological changes,Annexin V-PI flow cytometry was used to analyze cell apoptosis,and RT-PCR and Western blot method were used to detect the mRNA and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and farnesoid X receptor (FXR),respectively.Results MTT assay showed that strong cytotoxicity of cell line MCF-7 was induced after administration of osthole for 72 h in a dose-dependent manner.Especially,the maximum inhibitory rate,73.0 ％ appeared in the 200 μmol/L group.HE staining showed that the number of MCF-7 cells decreased,hyperchromatic nuclei and apoptotic bodies appeared after treatment with osthole for 72 h in a significant dose-effect manner.Flow cytometric analysis revealed that osthole could induce extensive apoptosis in MCF-7 cultures after treatment for 72 h compared with normal group (P ＜ 0.05,P ＜ 0.01).In particular,when the concentration of osthole reached 50 μmol/L,the proportion of early apoptotic cells was significantly increased in a dose-dependent manner (P ＜ 0.01),especially.The maximum apoptosis rate (46.2±9.0) ％ appeared in the 200 μmol/L group,which was consistent with the results obtained from MTT assays.Moreover,osthole could significantly increased PPARγand FXR mRNA and protein expressions (P ＜ 0.01).Conclusion These data suggest that osthole could inhibit the proliferation of breast cancer MCF-7 cells and promote its apoptosis,which might be associated with the regulation of PPARγ and FXR-mediated target genes involved in cell growth and metabolism.