Qin Qin, Chen Hui, Xu Huazhong, Zhang Xiaowen, Chen Junqiang, Zhang Chi, Liu Jia, Xu Liping, Sun Xinchen
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
J Cancer. 2023 Feb 5;14(3):454-463. doi: 10.7150/jca.76671. eCollection 2023.
Radioresistance is a main reason for local recurrence of esophageal squamous cell carcinoma (ESCC). Forkhead box M1 (FoxM1) is implicated in cancer progression and chemoresistance. This study aims to determine the role of FoxM1 in ESCC radioresistance. We found that FoxM1 protein was upregulated in ESCC tissues compared with adjacent normal tissues. assays revealed that following irradiation, Eca-109, TE-13, and KYSE-150 cells had increased levels of FoxM1 protein. FoxM1 knockdown resulted in significantly reduced colony formation and increased cell apoptosis following irradiation. Moreover, FoxM1 knockdown induced ESCC cells to accumulate in the radiosensitive G2 /M phase and impeded the repair of radiation-induced DNA damage. Mechanistic studies indicated that radiosensitization of ESCC enhanced by FoxM1 knockdown was associated with increased BAX/BCL2 ratio as well as downregulated Survivin and XIAP, followed by the activation of both extrinsic and intrinsic apoptosis pathways. In xenograft mouse model, the combination of radiation and FoxM1-shRNA led to a synergistic anti-tumor effect. In conclusion, FoxM1 is a promising target to enhance radiosensitivity of ESCC.
放射抗性是食管鳞状细胞癌（ESCC）局部复发的主要原因。叉头框M1（FoxM1）与癌症进展和化疗抗性有关。本研究旨在确定FoxM1在ESCC放射抗性中的作用。我们发现，与相邻正常组织相比，ESCC组织中FoxM1蛋白上调。实验表明，照射后，Eca-109、TE-13和KYSE-150细胞中FoxM1蛋白水平升高。敲低FoxM1导致照射后集落形成显著减少，细胞凋亡增加。此外，敲低FoxM1诱导ESCC细胞在放射敏感的G2/M期积累，并阻碍辐射诱导的DNA损伤修复。机制研究表明，敲低FoxM1增强的ESCC放射增敏作用与BAX/BCL2比值增加以及Survivin和XIAP下调有关，随后激活外源性和内源性凋亡途径。在异种移植小鼠模型中，放疗与FoxM1-shRNA联合使用产生了协同抗肿瘤作用。总之，FoxM1是提高ESCC放射敏感性的一个有前景的靶点。
