Vitamin D-induced vitamin D receptor expression induces tamoxifen sensitivity in MCF-7 stem cells via suppression of Wnt/β-catenin signaling. Issue 6 (7th December 2018)

• Record Type: Journal Article
• Authors: Zheng, Wei; Duan, Bofeng; Zhang, Qian; Ouyang, Linna; Peng, Wei; Qian, Fuyong; Wang, Yibin; Huang, Shiting
• Is Part Of: Bioscience reports. Volume 38:Issue 6(2018)
• Publication Date: 2018-12-07
• Subjects: Breast cancers -- Cancer stem cells -- Chemotherapy resistance -- Tamoxifen -- Vitamin D receptor; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20180595
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : Objective: Cancer stem cells (CSCs) are responsible for the drug resistance of breast cancers. Vitamin D deficiency promotes tumor resistance. The present study examined the effect of vitamin D and vitamin D receptor (VDR) expression on the tamoxifen resistance of CSCs.Methods: MCF-7 cells were treated with 1, 25(OH)2 D3 and their levels of VDR expression, viability, and apoptosis were detected. CD133 + MCF-7 stem cells were identified and transfected with a VDR-overexpression plasmid. The tamoxifen concentration that reduced MCF-7 cell viability by 50% (IC50 ) was determined. The activation of Wnt/β-catenin signaling was also investigated.Results: Vitamin D reduced the viability of MCF-7 cells and promoted their apoptosis. Vitamin D enhanced VDR expression and induced DNA damage. When CD133 + stem cells were separated from MCF-7 cells, the IC50 of tamoxifen for stem cells was significantly higher than that of parental MCF-7 cells, suggesting a higher tamoxifen resistance in MCF-7 stem cells. Levels of VDR expression and Wnt/β-catenin signaling in CD133 + cells were markedly lower and higher than those in CD133 − cells, respectively. Stem cells transfected with VDR overexpression plasmids showed decreased tamoxifen IC50 values, viability, spheroid formation, and expression of Wnt and β-catenin proteins when compared with control cells. Cell apoptosis was increased by transfection with a VDR overexpression plasmid. Finally, the inhibitory effects induced by VDR overexpression could be reversed by the VDR inhibitor, calcifediol.Conclusion: Stem cells contributed to the tamoxifen resistance of MCF-7 cells. Vitamin D-induced VDR expression increased the sensitivity of MCF-7 stem cells to tamoxifen by inhibiting Wnt/β-catenin signaling.