title: 1,25-Dihydroxyvitamin D3 alleviates salivary adenoid cystic carcinoma progression by suppressing GPX1 expression through the NF-κB pathway.
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.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Zixian
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Sun Yat‑sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Gan
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Zhuojian
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000737:chemistry; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry; D000094765:Glutathione Peroxidase GPX1
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D034741:RNA, Small Interfering; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D005979:Glutathione Peroxidase; D014568:Urokinase-Type Plasminogen Activator; D002945:Cisplatin; D000094765:Glutathione Peroxidase GPX1