MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer

Clin Oral Investig. 2018 Apr;22(3):1477-1486. doi: 10.1007/s00784-017-2242-8. Epub 2017 Oct 15.

Abstract

Objective: The objective of this study is to investigate the roles of melanoma-associated antigens (MAGEs) in the cisplatin treatment of head and neck cancer.

Materials and methods: We assessed the efficacy of cisplatin in a set of four head and neck cancer cell lines using a crystal violet assay. The MAGE-A expression in all cell lines was measured with RT-qPCR. The correlation between MAGE-A expression and cisplatin efficacy was investigated using Spearman's correlation analysis. Furthermore, we established a cell line with stable overexpression of MAGE-A11 and determined influence on proliferation, cisplatin efficacy and cell apoptosis. In this cell line, the effects of cisplatin were assessed using either crystal violet assays or flow cytometry (Annexin V).

Results: For MAGE-A11, we observed the highest correlation (r = 1.000, p = 0.0417) with low cisplatin efficacy. Stable overexpression of MAGE-A11 resulted in no changes in proliferation, but in lower cisplatin cytotoxicity and lower rates of apoptosis. Also, mouse double minute 2 homolog (MDM2) expression was induced by MAGE-A11 overexpression.

Conclusion: We provide evidence that MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer.

Clinical relevance: Our study underscores the negative predictive role of MAGE-A11 expression in head and neck cancer.

Keywords: Cisplatin; Head and neck cancer; Mage-A11; Melanoma-associated antigens.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Female
  • Flow Cytometry
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • MAGEA11 protein, human
  • Neoplasm Proteins
  • Cisplatin