1. MART-10, a 1α,25(OH)2D3 Analog, Potently Represses Metastasis of ER+ Breast Cancer Cells with VEGF-A Overexpression
- Author
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Masashi Takano, Sheng-Fong Kuo, Chun-Nan Yeh, Horng-Heng Juang, Atsushi Kittaka, Jong-Hwei S. Pang, Li-Wei Chen, Kun-Chun Chiang, Tai C. Chen, Ta-Sen Yeh, and Ming-Huang Chen
- Subjects
Cancer Research ,030219 obstetrics & reproductive medicine ,Angiogenesis ,Chemistry ,Cell migration ,General Medicine ,medicine.disease ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Oncology ,MCF-7 ,Neuropilin 1 ,Cancer cell ,medicine ,Cancer research ,030212 general & internal medicine ,Autocrine signalling - Abstract
Background Breast cancer ranks second in the list of cancer-related deaths for women. Even under multidisciplinary treatment, 25-50% of patients with breast cancer still ultimately develop metastasis, leading to poor prognosis. In addition to inducing angiogenesis, vascular endothelial growth factor-A (VEGF-A) is believed to directly increase cancer cell metastatic potential and overexpression of VEGF-A is associated with higher invasiveness of breast cancer. 1α,25(OH)2D3, the active form of vitamin D, and its analogs have been widely applied as anticancer agents in the past. Material and methods Western blot, migration and invasion assays, enzyme-linked immunosorbent assay, and immunofluorescent stain were applied in this study. Result VEGF-A increased cell migration and invasion in estrogen receptor-positive (ER+) breast cancer MCF-7 cells. VEGF-A induced an autocrine loop in MCF-7 cells as VEGF-A treatment increased both VEGF-A expression and secretion. The expression of VEGF receptor type 2 (VEGFR2) and neuropilin 1 was also up-regulated by VEGF-A in MCF-7 cells. In addition, F-actin synthesis and LIM domain kinase 1 (LIMK-1) phosphorylation were increased by VEGF-A. VEGF-A also increased β-catenin expression and nuclear translocation of both β-catenin and nuclear factor-ĸB (NF-ĸB), indicating increased β-catenin and NF-ĸB activity. 1α,25(OH)2D3 and MART-10, an analog of 1α,25(OH)2D3, effectively repressed VEGF-A-induced MCF-7 cell migration and invasion and other VEGF-A-induced effects on MCF-7 cells, with MART-10 being more potent than 1α,25(OH)2D3 Conclusion: MART-10 can be deemed as a promising agent for prevention and treatment of metastasis of ER+ breast cancer with VEGF-A overexpression.
- Published
- 2018
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