J Cancer 2023; 14(3):454-463. doi:10.7150/jca.76671 This issue Cite

Research Paper

FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis

Qin Qin1†, Hui Chen1†, Huazhong Xu2†, Xiaowen Zhang1, Junqiang Chen3, Chi Zhang1, Jia Liu1, Liping Xu1✉, Xinchen Sun1✉

1. Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
2. Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
3. Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China.
† Contributed equally.

Citation:
Qin Q, Chen H, Xu H, Zhang X, Chen J, Zhang C, Liu J, Xu L, Sun X. FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis. J Cancer 2023; 14(3):454-463. doi:10.7150/jca.76671. https://www.jcancer.org/v14p0454.htm
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Abstract

Graphic abstract

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. In vitro 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.

Keywords: FoxM1, esophageal cancer, radioresistance, apoptosis, IAPs


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APA
Qin, Q., Chen, H., Xu, H., Zhang, X., Chen, J., Zhang, C., Liu, J., Xu, L., Sun, X. (2023). FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis. Journal of Cancer, 14(3), 454-463. https://doi.org/10.7150/jca.76671.

ACS
Qin, Q.; Chen, H.; Xu, H.; Zhang, X.; Chen, J.; Zhang, C.; Liu, J.; Xu, L.; Sun, X. FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis. J. Cancer 2023, 14 (3), 454-463. DOI: 10.7150/jca.76671.

NLM
Qin Q, Chen H, Xu H, Zhang X, Chen J, Zhang C, Liu J, Xu L, Sun X. FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis. J Cancer 2023; 14(3):454-463. doi:10.7150/jca.76671. https://www.jcancer.org/v14p0454.htm

CSE
Qin Q, Chen H, Xu H, Zhang X, Chen J, Zhang C, Liu J, Xu L, Sun X. 2023. FoxM1 knockdown enhanced radiosensitivity of esophageal cancer by inducing apoptosis. J Cancer. 14(3):454-463.

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