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Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model
Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer. Vitamin D supplementation is getting popular due to its anti-tumor functions after conversion to its active form, 1α,25(OH)(2)D. Here, we show that dietary supplementation with 6 IU/g of vitamin D greatly suppressed ICC initiation and pr...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116525/ https://www.ncbi.nlm.nih.gov/pubmed/24939880 |
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author | Chiang, Kun-Chun Yeh, Chun-Nan Lin, Kun-Ju Su, Li-Jen Yen, Tzu-Chen Pang, Jong-Hwei S. Kittaka, Atsushi Sun, Chi-Chin Chen, Miin-Fu Jan, Yi-Yin Chen, Tai C. Juang, Horng-Heng Yeh, Ta-Sen |
author_facet | Chiang, Kun-Chun Yeh, Chun-Nan Lin, Kun-Ju Su, Li-Jen Yen, Tzu-Chen Pang, Jong-Hwei S. Kittaka, Atsushi Sun, Chi-Chin Chen, Miin-Fu Jan, Yi-Yin Chen, Tai C. Juang, Horng-Heng Yeh, Ta-Sen |
author_sort | Chiang, Kun-Chun |
collection | PubMed |
description | Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer. Vitamin D supplementation is getting popular due to its anti-tumor functions after conversion to its active form, 1α,25(OH)(2)D. Here, we show that dietary supplementation with 6 IU/g of vitamin D greatly suppressed ICC initiation and progression without apparent toxicity in a chemically induced rat model. Microarray analysis of rat ICC tissues showed vitamin D supplementation modulated the expressions of several unique genes, including lipocalin 2 (Lcn2), confirmed by RT-qPCR and immunohistochemical (IHC) staining. Further, 53 of 80 human ICC specimens (66%) exhibited high LCN2 expression and LCN2 knockdown in SNU308 cells decreased cell growth and migration, suggesting LCN2 be an oncogene in human ICC. As human ICC SNU1079 cells were treated by 1α,25(OH)(2)D(3), LCN2 expression and cell proliferation were attenuated. The downregulation of LCN2 expression was blunted when vitamin D receptor (VDR) was knocked down, implicating that the in vivo Lcn2 downregulation is a direct consequence of vitamin D supplementation Our results support the prevailing concept that vitamin D status is negatively associated with cancer incidence and mortality and suggest LCN2 may be a potential target against ICC. Further studies of application of vitamin D or its analogs against ICC are warranted. |
format | Online Article Text |
id | pubmed-4116525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-41165252014-08-04 Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model Chiang, Kun-Chun Yeh, Chun-Nan Lin, Kun-Ju Su, Li-Jen Yen, Tzu-Chen Pang, Jong-Hwei S. Kittaka, Atsushi Sun, Chi-Chin Chen, Miin-Fu Jan, Yi-Yin Chen, Tai C. Juang, Horng-Heng Yeh, Ta-Sen Oncotarget Research Paper Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer. Vitamin D supplementation is getting popular due to its anti-tumor functions after conversion to its active form, 1α,25(OH)(2)D. Here, we show that dietary supplementation with 6 IU/g of vitamin D greatly suppressed ICC initiation and progression without apparent toxicity in a chemically induced rat model. Microarray analysis of rat ICC tissues showed vitamin D supplementation modulated the expressions of several unique genes, including lipocalin 2 (Lcn2), confirmed by RT-qPCR and immunohistochemical (IHC) staining. Further, 53 of 80 human ICC specimens (66%) exhibited high LCN2 expression and LCN2 knockdown in SNU308 cells decreased cell growth and migration, suggesting LCN2 be an oncogene in human ICC. As human ICC SNU1079 cells were treated by 1α,25(OH)(2)D(3), LCN2 expression and cell proliferation were attenuated. The downregulation of LCN2 expression was blunted when vitamin D receptor (VDR) was knocked down, implicating that the in vivo Lcn2 downregulation is a direct consequence of vitamin D supplementation Our results support the prevailing concept that vitamin D status is negatively associated with cancer incidence and mortality and suggest LCN2 may be a potential target against ICC. Further studies of application of vitamin D or its analogs against ICC are warranted. Impact Journals LLC 2014-05-22 /pmc/articles/PMC4116525/ /pubmed/24939880 Text en Copyright: © 2014 Chiang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Chiang, Kun-Chun Yeh, Chun-Nan Lin, Kun-Ju Su, Li-Jen Yen, Tzu-Chen Pang, Jong-Hwei S. Kittaka, Atsushi Sun, Chi-Chin Chen, Miin-Fu Jan, Yi-Yin Chen, Tai C. Juang, Horng-Heng Yeh, Ta-Sen Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model |
title | Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model |
title_full | Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model |
title_fullStr | Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model |
title_full_unstemmed | Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model |
title_short | Chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model |
title_sort | chemopreventive and chemotherapeutic effects of dietary supplementation of vitamin d on cholangiocarcinoma in a chemical-induced animal model |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116525/ https://www.ncbi.nlm.nih.gov/pubmed/24939880 |
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