Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here, we report that concomitant treatment of HNSCCs with radiotherapy and mevalonate pathway inhibitors (statins) may overcome resistance. Proteomic profiling and comparison of radioresistant to radiosensitive HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin sensitized radioresistant SQ20B cells to ionizing radiation and reduced their clonogenic potential. Overall, this study reinforces the view that the mevalonate pathway is a promising therapeutic target in radioresistant HNSCCs.

中文翻译：

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甲羟戊酸途径活性作为头颈癌辐射敏感性的决定因素。

放射抗性是治疗头颈部鳞状细胞癌 (HNSCC) 的主要障碍。在这里，我们报告用放疗和甲羟戊酸途径抑制剂（他汀类药物）同时治疗 HNSCC 可能会克服耐药性。蛋白质组学分析和放射抗性与放射敏感性 HNSCC 的比较揭示了甲羟戊酸生物合成途径的差异调节。与这一发现一致，匹伐他汀对甲羟戊酸途径的抑制使抗辐射的 SQ20B 细胞对电离辐射敏感，并降低了它们的克隆形成潜力。总体而言，这项研究强化了甲羟戊酸途径是抗辐射 HNSCC 有希望的治疗靶点的观点。