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

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-2 alpha-(3-hydroxypropyl)-1 alpha,25(OH)(2)D-3), exerted potent antiproliferative effect on PDA in vitro and in vivo without causing hypercalcemia. Since metastasis is the major cause of FDA-related death, we therefore investigate the anti-metastasis effect of MART-10 on PDA. Our results showed that both 1 alpha,25(OH)(2)D-3 and MART-10 repressed migration and invasion of BxPC-3 and PANC cells with MART-10 much more potent than 1 alpha,25(OH)(2)D-3. 1 alpha,25(OH)(2)D-3 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 1 alpha,25(OH)(2)D-3 and MART-10 as determined by immunofluorescence stain. Both 1 alpha,25(OH)(2)D-3 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.