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Anticancer activity of 1, 25-(OH)2D3 against human breast cancer cell lines by targeting Ras/MEK/ERK pathway

Authors Zheng W, Cao L, Ouyang L, Zhang Q, Duan B, Zhou W, Chen S, Peng W, Xie Y, Fan Q, Gong D

Received 10 October 2018

Accepted for publication 4 December 2018

Published 22 January 2019 Volume 2019:12 Pages 721—732


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava

Wei Zheng,1 Lin Cao,2 Linna Ouyang,1 Qian Zhang,3 Bofeng Duan,1 Wei Zhou,4 Shan Chen,5 Wei Peng,1 Yi Xie,1 Qing Fan,6 Daoxing Gong7

1Department of Thyroid and Breast Surgery, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong 518112, China; 2Department of Breast Surgery, Maternal and Child Health Care Hospital of Hunan Province, Changsha, Hunan 410008, China; 3School of Clinical Medicine, Xiangnan University, Chenzhou, Hunan 423000, China; 4Department of Medical Examination, Zhuzhou Central Hospital, Zhuzhou, Hunan 412007, China; 5Department of General Surgery, The Third Hospital of Changsha, Changsha, Hunan 410013, China; 6Department of Gastrointestinal and Breast and Thyroid Surgery, Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha, Hunan 410100, China; 7Department of Surgery, The Medical School, University of South China, Hengyang, Hunan 421000, China

Purpose: Breast cancer is the most common cancer among women with ~1.67 million cases diagnosed annually worldwide, and ~1 in 37 women succumbed to breast cancer. Over the past decades, new therapeutic strategy has substantially improved the curative effect for women with breast cancer. However, the currently available ER-targeted and HER-2-based therapies are not effective for triple-negative breast cancer patients, which account for ~15% of total breast cancer cases.
Materials and methods: We reported that 1,25-(OH)2D3, a biologically active form of vitamin D3, exhibited a strong anticancer effects on the proliferation, migration, invasion, cell cycle arrest, and apoptosis of both ER-positive (MCF-7) and ER-negative breast cancer cells (MDA-MB-453).
Results: The anticancer effect of 1,25-(OH)2D3 was more potent compared to the classical chemotherapeutics tamoxifen in MDA-MB-453 cells. Furthermore, we also found that 1,25-(OH)2D3 decreased the expression of Ras and resulted in decrease of the phosphorylation of downstream proteins MEK and ERK1/2, indicating that 1,25-(OH)2D3 plays its anticancer roles through targeting the Ras/MEK/ERK signaling pathway. In addition, Ras overexpression abrogated 1,25-(OH)2D3-induced G0/G1 cell cycle arrest and apoptosis of breast cancer cells, as well as the suppression of proliferation, migration, and invasion. Our study suggested that 1,25-(OH)2D3 suppressed breast cancer tumorigenesis by targeting the Ras/MEK/ERK signaling pathway.
Conclusion: 1,25-(OH)2D3 might serve as a promising supplement for breast cancer drug therapy, especially for the ER-negative breast cancer and drug-resistant breast cancer.

Keywords: breast cancer, 1,25-(OH)2D3, ER-negative, cell apoptosis, cell proliferation

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