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醛缩酶 A 通过调节照射后糖酵解和 DNA 损伤促进宫颈癌放疗抵抗。

Aldolase A promotes cervical cancer cell radioresistance by regulating the glycolysis and DNA damage after irradiation.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Cancer Biol Ther. 2023 Dec 31;24(1):2287128. doi: 10.1080/15384047.2023.2287128. Epub 2023 Nov 27.

Abstract

Radioresistance is the major obstacle that affects the efficacy of radiotherapy which is an important treatment for cervical cancer. By analyzing the databases, we found that aldolase A (ALDOA), which is a key enzyme in metabolic reprogramming, has a higher expression in cervical cancer patients and is associated with poor prognosis. We detected the expression of ALDOA in the constructed cervical cancer radioresistance (RR) cells by repetitive irradiation and found that it was upregulated compared to the control cells. Functional assays were conducted and the results showed that the knockdown of ALDOA in cervical cancer RR cells inhibited the proliferation, migration, and clonogenic abilities by regulating the cell glycolysis. In addition, downregulation of ALDOA enhanced radiation-induced apoptosis and DNA damage by causing G2/M phase arrest and further promoted radiosensitivity of cervical cancer cells. The functions of ALDOA in regulating tumor radiosensitivity were also verified by the mouse tumor transplantation model . Therefore, our study provides new insights into the functions of ALDOA in regulating the efficacy of radiotherapy and indicates that ALDOA might be a promising target for enhancing radiosensitivity in treating cervical cancer patients.

摘要

放射抗拒是影响宫颈癌放射治疗效果的主要障碍,放射治疗是宫颈癌的重要治疗方法。通过分析数据库,我们发现醛缩酶 A(ALDOA)作为代谢重编程的关键酶,在宫颈癌患者中表达较高,与预后不良相关。我们通过反复照射构建了宫颈癌放射抵抗(RR)细胞,检测到 ALDOA 的表达水平上调,与对照细胞相比。功能分析结果表明,下调 ALDOA 可通过调节细胞糖酵解抑制宫颈癌 RR 细胞的增殖、迁移和集落形成能力。此外,下调 ALDOA 通过引起 G2/M 期阻滞和进一步增强癌细胞的放射敏感性,促进放射诱导的细胞凋亡和 DNA 损伤。通过小鼠肿瘤移植模型也验证了 ALDOA 在调节肿瘤放射敏感性方面的功能。因此,我们的研究为 ALDOA 调节放射治疗效果的功能提供了新的见解,并表明 ALDOA 可能是提高宫颈癌患者放射敏感性的有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03b2/10761068/f5f81d29d25b/KCBT_A_2287128_F0001_OC.jpg

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