Abstract
1,25-Dihydroxyvitamin D3 (1,25D3) is the active form of vitamin D with antineoplastic effects. The glutathione peroxidase-1 (GPX1) gene is associated with tumour progression. The present study aimed to explore the role of GPX1 in 1,25D3-mediated progression of salivary adenoid cystic carcinoma (SACC). Downregulating GPX1 expression inhibited SACC cell proliferation, chemoresistance, motility, and uPA secretion, but promoted apoptosis via the NF-κB pathway. Pre-processing 1,25D3 inhibited expression of NF-κB/GPX1/uPA, which subsequently suppressed cell motility and cisplatin-resistance in ACC-2 cells. In conclusion, 1,25D3 works as a modifier of NF-κB/GPX1/uPA expression, inhibiting cisplatin-resistance and cell invasive ability of SACC cells. The present study comprehensively elucidated the potential mechanism underlying the effects of vitamin D on chemoresistance and invasive potential in SACC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Carcinoma, Adenoid Cystic / drug therapy
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Carcinoma, Adenoid Cystic / metabolism
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Carcinoma, Adenoid Cystic / pathology*
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Cisplatin / chemistry
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Disease Progression
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Drug Resistance, Neoplasm
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Gene Expression Regulation, Neoplastic*
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Glutathione Peroxidase / metabolism*
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Glutathione Peroxidase GPX1
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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NF-kappa B p50 Subunit / metabolism*
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Neoplasm Invasiveness
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Neoplasm Transplantation
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RNA, Small Interfering / metabolism
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Salivary Gland Neoplasms / drug therapy
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Salivary Gland Neoplasms / metabolism
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Salivary Gland Neoplasms / pathology*
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Urokinase-Type Plasminogen Activator / metabolism
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Vitamin D / analogs & derivatives*
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Vitamin D / chemistry
Substances
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NF-kappa B p50 Subunit
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NFKB1 protein, human
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RNA, Small Interfering
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dihydroxy-vitamin D3
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Vitamin D
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Glutathione Peroxidase
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Urokinase-Type Plasminogen Activator
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Cisplatin
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Glutathione Peroxidase GPX1