Stefan Hartmann1,2, Leonie Zwick3, Mario J J Scheurer3, Andreas R Fuchs3, Roman C Brands3,4, Axel Seher3, Hartmut Böhm3, Alexander C Kübler3, Urs D A Müller-Richter3. 1. Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany. hartmann_s2@ukw.de. 2. Interdisciplinary Center for Clinical Research, University Hospital Würzburg, Josef-Schneider-Straße 2, 97070, Würzburg, Germany. hartmann_s2@ukw.de. 3. Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany. 4. Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Josef-Schneider-Str. 6, 97070, Würzburg, Germany.
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.
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 cisplatincytotoxicity 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.
Entities:
Keywords:
Cisplatin; Head and neck cancer; Mage-A11; Melanoma-associated antigens
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