The vitamin D analog, MART-10, represses metastasis potential via downregulation of epithelial-mesenchymal transition in pancreatic cancer cells.

Abstract

Pancreatic cancer (PDA) is a devastating disease and there is no effective treatment available at present. To develop new regiments against PDA is urgently needed. Previously we have shown that vitamin D analog, MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3), exerted potent antiproliferative effect on PDA in vitro and in vivo without causing hypercalcemia. Since metastasis is the major cause of PDA-related death, we therefore investigate the anti-metastasis effect of MART-10 on PDA. Our results showed that both 1α,25(OH)2D3 and MART-10 repressed migration and invasion of BxPC-3 and PANC cells with MART-10 much more potent than 1α,25(OH)2D3. 1α,25(OH)2D3 and MART-10 inhibited epithelial-mesenchymal transition (EMT) in pancreatic cancer cells through downregulation of Snail, Slug, and Vimentin expression in BxPC-3 and PANC cells. MART-10 further blocked cadherin switch (from E-cadherin to N-cadherin) in BxPC-3 cells. The F-actin synthesis in the cytoplasm of BxPC-3 cells was also repressed by 1α,25(OH)2D3 and MART-10 as determined by immunofluorescence stain. Both 1α,25(OH)2D3 and MART-10 decreased MMP-2 and -9 secretion in BxPC-3 cells as determined by western blot and zymography. Collectively, MART-10 should be deemed as a promising regimen against PDA.

• Authors: Kun-Chun Chiang, Chun-Nan Yeh, Jun-Te Hsu, Yi-Yin Jan, Li-Wei Chen, Sheng-Fong Kuo, Masashi Takano, Atsushi Kittaka, Tai C Chen, Wen-Tsung Chen, Jong-Hwei S Pang, Ta-Sen Yeh, Horng-Heng Juang
• Journal: Cancer letters (Cancer Lett) Vol. 354 Issue 2 Pg. 235-44 (Nov 28 2014) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 25149065 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3
• Antigens, CD
• Antineoplastic Agents
• CDH2 protein, human
• Cadherins
• Cholecalciferol
• MMP13 protein, human
• Matrix Metalloproteinase 13
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Antigens, CD (metabolism)
• Antineoplastic Agents (pharmacology)
• Cadherins (metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cholecalciferol (analogs & derivatives, pharmacology)
• Down-Regulation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• Matrix Metalloproteinase 13 (biosynthesis)
• Matrix Metalloproteinase 2 (biosynthesis)
• Matrix Metalloproteinase 9 (biosynthesis)
• Neoplasm Metastasis
• Pancreatic Neoplasms (drug therapy, enzymology, pathology)