Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450000, Henan, China.
China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450003, Henan, China.
Cell Death Dis. 2022 Feb 25;13(2):189. doi: 10.1038/s41419-022-04642-x.
Esophageal squamous cell carcinoma (ESCC), a malignant neoplasm with high incidence, is a severe global public health threat. The current modalities used for treating ESCC include surgery, chemotherapy, and radiotherapy. Although ESCC management and treatment strategies have improved over the last decade, the overall 5-year survival rate remains <20%. Therefore, the identification of novel therapeutic strategies that can increase ESCC patient survival rates is urgently needed. Oxethazaine, an amino-amide anesthetic agent, is mainly prescribed in combination with antacids to relieve esophagitis, dyspepsia, and other gastric disorders. In the present study, we found that oxethazaine inhibited the proliferation and migration of esophageal cancer cells. According to the results of in vitro screening and binding assays, oxethazaine binds directly to AURKA, suppresses AURKA activity, and inhibits the downstream effectors of AURKA. Notably, we found that oxethazaine suppressed tumor growth in three patient-derived esophageal xenograft mouse models and tumor metastasis in vivo. Our findings suggest that oxethazaine can inhibit ESCC proliferation and metastasis in vitro and in vivo by targeting AURKA.
食管鳞状细胞癌（ESCC）是一种发病率较高的恶性肿瘤，是严重的全球公共卫生威胁。目前用于治疗 ESCC 的方法包括手术、化疗和放疗。尽管在过去十年中 ESCC 的管理和治疗策略有所改善，但总体 5 年生存率仍<20%。因此，迫切需要确定能够提高 ESCC 患者生存率的新治疗策略。奥昔卡因，一种氨基酰胺麻醉剂，主要与抗酸剂联合用于缓解食管炎、消化不良和其他胃部疾病。在本研究中，我们发现奥昔卡因抑制食管癌细胞的增殖和迁移。根据体外筛选和结合测定的结果，奥昔卡因直接与 AURKA 结合，抑制 AURKA 活性，并抑制 AURKA 的下游效应物。值得注意的是，我们发现奥昔卡因在三种患者来源的食管异种移植小鼠模型中抑制肿瘤生长，并在体内抑制肿瘤转移。我们的研究结果表明，奥昔卡因通过靶向 AURKA 可在体外和体内抑制 ESCC 的增殖和转移。
