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The Therapeutic Effect of Vitamin D 3 in Conjunction with Cathelicidin for Gastric Cancer
Author(s) -
Li Mingxing,
Wu William,
Zhang Lin,
Shen Jing,
Chan Ruby,
Chan Franky,
Cho Chi Hin
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.629.15
Subject(s) - cathelicidin , cancer , cancer cell , cancer research , medicine , cell cycle , calcitriol receptor , in vivo , vitamin d and neurology , viability assay , mtt assay , cell growth , flow cytometry , western blot , pharmacology , cell , chemistry , receptor , biology , immunology , biochemistry , innate immune system , microbiology and biotechnology , gene
Objective Our research aims to investigate the therapeutic effects of vitamin D 3 in gastric cancer and its relationship with cathelicidin (LL37), a host defense and antimicrobial peptide , in mediating the anticancer action of vitamin D 3 both in vitro and in vivo.Methods To assess the inhibitory action of vitamin D 3 on gastric cancer cells (TMK1), MTT assay was used to measure the cell viability and flow cytometry was employed to detect the cell cycle distribution. The expressions of p21, vitamin D receptor (VDR), LL37 and LC3BII were determined by Western‐blot. An model of orthotopic gastric cancer was also established in nude mice to evaluate the anticancer action of vitamin D 3 in vivo . Results 1α,25(OH) 2 vitamin D 3 (1,25D 3 ), the active form of vitamin D 3 , could significantly inhibit the proliferation and induce cell cycle arrest through stimulating the expression of p21 in TMK1 but not in the normal gastric epithelial cells (HFE145). This vitamin analogue also successfully induced the expression of LL37 and provoked autophagy in TMK1. Knockdown of LL37 by siRNA abolished the anti‐proliferative effect of 1,25D 3 in gastric cancer cells. We further found that daily oral administration with vitamin D 3 significantly inhibited tumor growth in the orthotopic gastric cancer model. Conclusion Our results suggest that vitamin D 3 inhibits gastric cancer in a cathelicidin‐dependent manner and it could also function as a novel therapeutic agent for gastric cancer in the future. Acknowledgements: This study is supported in part by the General Research Fund from the Hong Kong Research Grant Council and the Health and Medical Research Fund from the Food and Health Bureau in Hong Kong.