1,25-Dihydroxyvitamin D3 suppresses gastric cancer cell growth through VDR- and mutant p53-mediated induction of p21.
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AbstractAims

Previous studies have indicated that vitamin D deficiency correlates with cancer risk and vitamin D potentiates antitumor effects in a variety of cancers. The antitumor effect of vitamin D on gastric cancer was rarely studied. We aimed to investigate the antitumor effect of vitamin D on gastric cancer and underlying mechanisms.

Main methods

We investigated the antitumor activity of the active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on gastric cancer cells (TMK1) and immortalized normal gastric cells (HFE145) by using MTT, colony formation and Flow cytometry assays. We demonstrated the important role of vitamin D receptor (VDR) and mutant p53 (mutp53) in mediating the antitumor action of 1,25(OH)2D3 by using siRNA, western-blot, immunofluorescent staining and immunoprecipitation assays.

Key findings

1,25(OH)2D3 could significantly inhibit proliferation and induce cell cycle arrest in TMK1 but not in HFE145. Furthermore, 1,25(OH)2D3 stimulated p21 expression and suppressed cyclin-dependent kinase 2 (CDK2) expression in TMK1 in a VDR-dependent manner. High levels of VDR in human gastric cancer tissues and cancer cell lines implicated that vitamin D could display more potent pharmacological action against malignant cells. Besides, mutp53 but not wild type p53 was essential for 1,25(OH)2D3-stimulated upregulation of p21 in gastric cancer cells. Indeed, mutp53 could stabilize nuclear VDR level through interaction with VDR.

Significance

Our results suggest that 1,25(OH)2D3 inhibits gastric cancer cell growth through VDR and mutp53 interaction followed by the modulation of p21/CDK2. We propose that vitamin D might be used for the prophylactic treatment for malignant diseases in the stomach.
All Author(s) ListMingxing LI, Longfei LI, Lin ZHANG, Wei HU, Jing SHEN, Zhangang XIAO, X. WU, Leung Franky CHAN, Chi Hin CHO
Journal nameLife Sciences
Year2017
Month6
Day15
Volume Number179
PublisherElsevier
Pages88 - 97
ISSN0024-3205
LanguagesEnglish-United Kingdom
Keywords1,25-Dihydroxyvitamin D(3), Gastric cancer, Mutant p53, VDR, p21

Last updated on 2020-22-01 at 01:31