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Astemizole promotes the anti-tumor effect of vitamin D through inhibiting miR-125a-5p-meidated regulation of VDR in HCC.

Authors: Xu, Junli  Wang, Yan  Zhang, Ya  Dang, Shan  He, Shuixiang 
Citation: Xu J, etal., Biomed Pharmacother. 2018 Nov;107:1682-1691. doi: 10.1016/j.biopha.2018.08.153. Epub 2018 Sep 8.
Pubmed: (View Article at PubMed) PMID:30257386
DOI: Full-text: DOI:10.1016/j.biopha.2018.08.153

Hepatocellular carcinoma (HCC) accounts for the fifth most common cancer worldwide. Vitamin D and antihistamines have been shown to play an anti-tumor role in various tumors. In the present study, we ought to investigate the synergistic effect of astemizole and Vitamin D in HCC cells. We showed that astemizole enhanced the anti-tumor effect of Vitamin D in HCC both in vitro and in vivo. Astemizole enhanced Vitamin D-induced decrease of cell viability and proliferation, increase of apoptosis, decrease of cell migration and invasion in HCC cells in vitro and decrease of tumor number, mass and incidence in HCC in vivo. Astemizole increased VDR expression both in HCC cells in vitro and in tumor tissues in vivo. Downregulation of VDR significantly inhibited the synergistic effect of Vitamin D and astemizole on HCC cell viability, proliferation, apoptosis, migration and invasion. Bioinformatics analysis identified that miR-125a-5p had a putative binding site in the 3'-UTR of VDR. miR-125a-5p mimics inhibited astemizole-induced increase of VDR and enhancement of the anti-tumor effect of Vitamin D in HCC. Reporter gene assay has confirmed that VDR was regulated by miR-125a-5p. miR-125a-5p inhibitors increased VDR expression and decreased cell viability and proliferation in HCC cells. Moreover, VDR and miR-125a-5p expression in tumor tissues in HCC patients were negatively correlated. We identified that inhibition of miR-125a-5p and subsequent upregulation of VDR was involved in astemizole-induced enhancement of the anti-tumor effect of Vitamin D in HCC. These results highlight the importance of combined treatment of astemizole and Vitamin D and provide novel insights into the role of miR-125a-5p-VDR signaling in HCC.

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CRRD ID: 21403677
Created: 2020-03-09
Species: All species
Last Modified: 2020-03-09
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.