title: Low-dose decitabine induces MAGE-A expression and inhibits invasion via suppression of NF-κB2 and MMP2 in Eca109 cells.
abstract: Decitabine, a demethylating drug, is the first-line treatment for myelodysplastic syndromes and gains better overall survival, which is based on epigenetic mechanism. Activated by promoter demethylation, melanoma-associated antigens-A (MAGE-A), cancer-testis antigens are attractive targets for immunotherapy. Our purpose was to investigate whether decitabine could show anti-tumor effects for esophageal cancer and explore its mechanism. In addition, we aimed to examine its modulation for most MAGE-A members. The results showed the baseline expression were MAGE-A2, -3,-9, and -10 in Eca109 cells and decitabine (0.5 μM) could induce MAGE-A8 and -A4 whereas reduce MAGE-A9 and -A10. Moreover, decitabine (0.5 μM) inhibited cell proliferation, migration and invasive ability by 15%, 34% and 47.2%, respectively and decreased expressions of NF-κB2 and MMP2. Our results demonstrated that low-dose decitabine induced the expression of MAGE-A8 and -A4, and inhibited cell invasion through decreasing expression of MMP2 and NF-κB2, which provides possibilities for combing decitabine with immunotherapy targeting MAGE-A to treat advanced esophageal squamous cell carcinoma.
authors.affiliation: Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China; Center for Disease Control and Prevention of Shijiazhuang, Shijiazhuang, Hebei 050011, PR China.
authors.forename: Wei-hua
authors.initials: WH
authors.lastname: Liu
authors.affiliation: Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China.
authors.forename: Mei-xiang
authors.initials: MX
authors.lastname: Sang
authors.affiliation: Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China; Department of Oncology, The Third Hospital of Hebei Medical University, Shijiazhuang, HeBei 050011, PR China.
authors.forename: Shu-yun
authors.initials: SY
authors.lastname: Hou
authors.affiliation: Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China. Electronic address: baoenshan62@hotmail.com.
authors.forename: Bao-en
authors.initials: BE
authors.lastname: Shan
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077209:Decitabine; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D052003:NF-kappa B p52 Subunit / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis
chemical_list: D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; C095204:MAGEA4 protein, human; D052003:NF-kappa B p52 Subunit; D009363:Neoplasm Proteins; D000077209:Decitabine; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D001374:Azacitidine
keywords: Decitabine; Esophageal squamous cell carcinoma; Immunotherapy; Invasion; MAGE-A