RGD Reference Report - Chemopreventive and chemotherapeutic effect of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model. - Rat Genome Database

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Chemopreventive and chemotherapeutic effect of dietary supplementation of vitamin D on cholangiocarcinoma in a Chemical-Induced animal model.

Authors: 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 
Citation: Chiang KC, etal., Oncotarget. 2014 Jun 15;5(11):3849-61. doi: 10.18632/oncotarget.2000.
RGD ID: 126790491
Pubmed: PMID:24939880   (View Abstract at PubMed)
PMCID: PMC4116525   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.2000   (Journal Full-text)

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer. Vitamin D, a pro-hormone, is getting popular due to its hormone-like functions after converted to its active form, 1α,25(OH)2D3. 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)2D3, 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 analog against ICC are warranted.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
intrahepatic cholangiocarcinoma treatmentISOLcn2 (Rattus norvegicus)126790491; 126790491 RGD 
intrahepatic cholangiocarcinoma  IEP 126790491Protein:increased expression:bile ductRGD 
intrahepatic cholangiocarcinoma treatmentIDA 126790491 RGD 
intrahepatic cholangiocarcinoma  ISOLCN2 (Homo sapiens)126790491; 126790491Protein:increased expression:bile ductRGD 

Objects Annotated

Genes (Rattus norvegicus)
Lcn2  (lipocalin 2)

Genes (Mus musculus)
Lcn2  (lipocalin 2)

Genes (Homo sapiens)
LCN2  (lipocalin 2)


Additional Information