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

被引:7
|
作者
Zhou, Junying [1 ]
Lei, Ningjing [2 ]
Qin, Bo [3 ]
Chen, Mengyu [1 ]
Gong, Shuai [4 ]
Sun, Hao [5 ]
Qiu, Luojie [1 ]
Wu, Fengling [1 ]
Guo, Ruixia [1 ]
Ma, Qian [1 ]
Li, Yong [6 ,7 ]
Chang, Lei [1 ]
机构
[1] Zhengzhou Univ, Dept Obstet & Gynecol, Affiliated Hosp 1, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Sch Basic Med Sci, Zhengzhou, Henan, Peoples R China
[3] Zhengzhou Univ, Translat Med Ctr, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China
[4] Zhengzhou Univ, Dept Oncol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China
[5] Zhengzhou Univ, Dept Radiat Oncol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China
[6] St George Hosp, Canc Care Ctr, Kogarah, NSW, Australia
[7] UNSW Sydney, Sch Clin Med, St George & Sutherland Clin Campuses, Sydney, NSW, Australia
基金
中国国家自然科学基金;
关键词
ALDOA; cervical cancer; radiotherapy; radioresistance; glycolysis; DNA damage; AEROBIC GLYCOLYSIS; RADIOTHERAPY; METABOLISM; HIF-1;
D O I
10.1080/15384047.2023.2287128
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 in vivo. 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.
引用
收藏
页数:11
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