title: 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.affiliation: General Surgery Department, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
authors.affiliation: General Surgery Department, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan.
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.affiliation: General Surgery Department, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan.
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.affiliation: General Surgery Department, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan.
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Jan
authors.affiliation: Department of Gastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Sheng-Fong
authors.initials: SF
authors.lastname: Kuo
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
authors.affiliation: Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Tai C
authors.initials: TC
authors.lastname: Chen
authors.affiliation: National Kaohsiung University of Hospitality and Tourism, Hsiao-Kang, Kaohsiung, Taiwan.
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan.
authors.forename: Jong-Hwei S
authors.initials: JH
authors.lastname: Pang
authors.affiliation: General Surgery Department, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.affiliation: Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan Taoyuan, 333, Taiwan. Electronic address: hhj143@mail.cgu.edu.tw.
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*
chemical_list: C569618:19-nor-2-(3-hydroxypropyl)-1,25-dihydroxyvitamin D3; D015703:Antigens, CD; D000970:Antineoplastic Agents; C050361:CDH2 protein, human; D015820:Cadherins; D002762:Cholecalciferol; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: BxPC-3; EMT; MART-10; Metastasis; Pancreatic cancer; Vitamin D analog