Apatinib induces apoptosis of breast cancer cells by redistribution of Fas into lipid rafts

Apatinib,an oral anti-angiogenic agent,has been shown to have anti-cancer effects for several cancer cell types.However,little is known about the direct anti-tumor activity of apatinib for breast cancer cells.Herein,the direct effect of apatinib on breast cancer cells and its mechanism of action were assessed.Cell viability was measured with a Cell Counting Kit-8.Cell apoptosis was assessed by flow cytometry.The expression of caspase-8 and the cleavage of poly ADP ribose polymerase were assessed by Western blotting analysis.Lipid rafts and Fas distribution were determined by immunofluorescence microscopy.Apatinib suppressed breast cancer cell proliferation in a dose-dependent manner.Furthermore,apatinib enhanced the aggregation of lipid rafts and the redistribution of Fas into lipid rafts.Pretreatment with methyl-β-cyclodextrin,a cholesterol-sequestering agent,significantly reversed Fas redistribution and apatinib-induced apoptosis.In conclusion,these results demonstrated that apatinib induced apoptosis of breast cancer cells partially through recruitment of Fas into lipid rafts.

A Promising Predictor of the Efficacy of Endocrine Therapy for Breast Cancer: 14-3-3-zeta

Objective 14-3-3-zeta protein has been found to be associated with survival signaling in cancer.However,prognostic value and the predictive effect of its gene expression for determining the efficacy of endocrine therapy in breast cancer are unclear.Methods The differential 14-3-3-zeta gene expression between cancer and normal tissue was assayed using ONCOMINE database analysis.The correlation between 14-3-3-zeta gene and proliferative/metastasis-associated genes was analyzed using Breast Cancer Gene-Expression Miner v4.1(bc-Gen Ex Miner v4.1).The prognostic value of its expression in breast cancer was analyzed using bc-Gen Ex Miner v4.1 and Kaplan-Meier Plotter.Results The 14-3-3-zeta gene expression was elevated in breast cancer tissue compared with normal breast tissue,which was higher in invasive ductal breast cancer than in ductal breast cancer in situ.It was also positively correlated with the degree of malignancy and the clinical stage of breast cancer and with some proliferative genes.A high level of 14-3-3-zeta expression was predictive of shorter relapse-free survival(RFS)in ER-positive but not ER-negative breast cancer.Further analysis showed the association of high 14-3-3-zeta expression and a shorter RFS in endocrine therapy or tamoxifen-only-treated population,regardless of whether chemotherapy had been used.Conclusion 14-3-3-zeta gene expression is upregulated and associated with a relatively high degree of malignancy and late clinical stage in breast cancer.It is a promising prognostic factor for ER-positive breast cancer and a predictor of the efficacy of endocrine therapy.