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: Wei-hua Liu, Mei-xiang Sang, Shu-yun Hou, Chao Zhang, Bao-en Shan
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 68 Issue 6 Pg. 745-50 (Jul 2014) ISSN: 1950-6007 [Electronic] France
• PMID: 25123082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Antimetabolites, Antineoplastic
• MAGEA4 protein, human
• NF-kappa B p52 Subunit
• Neoplasm Proteins
• Decitabine
• MMP2 protein, human
• Matrix Metalloproteinase 2
• Azacitidine

Topics

• Antigens, Neoplasm (biosynthesis)
• Antimetabolites, Antineoplastic (administration & dosage)
• Azacitidine (administration & dosage, analogs & derivatives)
• Carcinoma, Squamous Cell (drug therapy, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Decitabine
• Esophageal Neoplasms (drug therapy, metabolism)
• Esophageal Squamous Cell Carcinoma
• Humans
• Matrix Metalloproteinase 2 (biosynthesis)
• NF-kappa B p52 Subunit (antagonists & inhibitors, biosynthesis)
• Neoplasm Invasiveness
• Neoplasm Proteins (biosynthesis)