1. Academic Validation
  2. Vitamin D-induced vitamin D receptor expression induces tamoxifen sensitivity in MCF-7 stem cells via suppression of Wnt/β-catenin signaling

Vitamin D-induced vitamin D receptor expression induces tamoxifen sensitivity in MCF-7 stem cells via suppression of Wnt/β-catenin signaling

  • Biosci Rep. 2018 Dec 7;38(6):BSR20180595. doi: 10.1042/BSR20180595.
Wei Zheng 1 Bofeng Duan 2 Qian Zhang 3 Linna Ouyang 2 Wei Peng 2 Fuyong Qian 2 Yibin Wang 2 Shiting Huang 2
Affiliations

Affiliations

  • 1 Department of Breast and Thyroid Surgery, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong 518112, China SZTPHZhengwei@hotmail.com.
  • 2 Department of Breast and Thyroid Surgery, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong 518112, China.
  • 3 Teaching and Research Section of Surgery, Xiangnan University Affiliated Hospital, Chenzhou, Hunan 423000, China.
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)2D3 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.

Keywords

Breast cancers; Cancer stem cells; Chemotherapy resistance; Tamoxifen; Vitamin D receptor.

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