CD39 inhibitor (POM-1) enhances radiosensitivity of esophageal squamous cell carcinoma (ESCC) cells by promoting apoptosis through the Bax/Bcl-2/Caspase 9/Caspase 3 pathway.

Autor: Wang Y; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Zhang R; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Huang X; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., He X; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Geng S; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Pan S; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Guo W; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Liu X; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Dang Y; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Qu J; The Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: qujingkun@xjtu.edu.cn., Ma H; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: mhbxian@126.com., Zhao X; Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: xixizhao@xjtu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt B), pp. 113242. Date of Electronic Publication: 2024 Sep 24.
DOI: 10.1016/j.intimp.2024.113242
Abstrakt: CD39 inhibitor (sodium polyoxotungstate, POM-1) has been reported to have antitumor effects. However, the synergistic effect of POM-1 with radiotherapy requires further elucidation. This study aimed to investigate the role and the molecular mechanism of POM-1 in esophageal squamous cell carcinoma (ESCC) radiosensitization. Firstly, the expression of CD39 in ESCC cells and normal esophageal epithelial cells were detected. Then radioresistant ESCC cells (Eca109R and KYSE150R) were constructed and CD39 expression was analyzed. Furthermore, the effect of POM-1 on radiosensitivity for parent cells and radioresistant cells were observed. Then, we analyzed the effect of POM-1 and CD39 siRNA on radiotherapy-induced apoptosis and determined whether POM-1 modulated the radioresistance of ESCC cells depending on the apoptotic signaling pathway. Finally, we validated the synergistic effect of POM-1 combined with radiotherapy in vivo. Our results showed that CD39 was highly expressed in ESCC cells and radioresistant ESCC cells (p < 0.05). POM-1 reduced radioresistance and proliferation of parent cells and radioresistant cells (p < 0.05). Further mechanistic exploration showed that inhibition of CD39 promoted radiation-induced apoptosis (p < 0.05). Bax knockdown reversed the effect of POM-1 on ESCC cells (p < 0.01). Animal experiments also validated that radiotherapy combined with POM-1 enhanced tumor inhibition in vivo (p < 0.05). These results suggested that POM-1 had synergistic effect with radiotherapy by enhancing cell apoptosis through Bax/Bcl-2 signal pathway in ESCC. The combination of POM-1 and radiotherapy is expected to enhance the anti-tumor effect in ESCC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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