Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
Interdisciplinary Center for Clinical Research, University Hospital Würzburg, Josef-Schneider-Straße 2, 97070, Würzburg, Germany.
Clin Oral Investig. 2018 Apr;22(3):1477-1486. doi: 10.1007/s00784-017-2242-8. Epub 2017 Oct 15.
The objective of this study is to investigate the roles of melanoma-associated antigens (MAGEs) in the cisplatin treatment of head and neck cancer.
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).
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.
We provide evidence that MAGE-A11 expression contributes to cisplatin resistance in head and neck cancer.
Our study underscores the negative predictive role of MAGE-A11 expression in head and neck cancer.
本研究旨在探讨黑色素瘤相关抗原（MAGEs）在顺铂治疗头颈部癌症中的作用。
我们使用结晶紫测定法评估了顺铂在四组头颈部癌细胞系中的疗效。使用 RT-qPCR 测量所有细胞系中的 MAGE-A 表达。使用 Spearman 相关分析研究 MAGE-A 表达与顺铂疗效之间的相关性。此外，我们建立了 MAGE-A11 稳定过表达的细胞系，并确定其对增殖、顺铂疗效和细胞凋亡的影响。在该细胞系中，使用结晶紫测定法或流式细胞术（Annexin V）评估顺铂的作用。
对于 MAGE-A11，我们观察到与低顺铂疗效的相关性最高（r=1.000，p=0.0417）。MAGE-A11 的稳定过表达导致增殖无变化，但顺铂细胞毒性降低，细胞凋亡率降低。此外，MAGE-A11 过表达诱导了鼠双微体 2 同源物（MDM2）的表达。
我们提供的证据表明，MAGE-A11 表达有助于头颈部癌症的顺铂耐药性。
我们的研究强调了 MAGE-A11 表达在头颈部癌症中具有负预测作用。
