TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response.

Autor: Pang SG; Department of Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., Zhang X; Department of Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., Li ZX; Department of Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., He LF; Department of Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., Chen F; Department of Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., Liu ML; Department of Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., Huang YZ; Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., Mo JM; Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., Luo KL; Department of Oncology, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China., Xiao JJ; Cancer Research Institute, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. xjjuan2006@glmc.edu.cn.; Translational Medical Center, Huaihe Hospital, Henan University, Kaifeng, 475000, China. xjjuan2006@glmc.edu.cn., Zhu F; Translational Medical Center, Huaihe Hospital, Henan University, Kaifeng, 475000, China. fengzhu@glmc.edu.cn.; Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. fengzhu@glmc.edu.cn.
Jazyk: angličtina
Zdroj: Current medical science [Curr Med Sci] 2024 Jun; Vol. 44 (3), pp. 545-553. Date of Electronic Publication: 2024 Jun 20.
DOI: 10.1007/s11596-024-2884-0
Abstrakt: Objective: Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer. However, the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer (CRC) cells is unclear. This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells.
Methods: The expression of TOPK was detected in CRC tissues by immunohistochemistry, and the effect of TOPK knockdown was detected in CRC cells by Western blotting. CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells. Furthermore, proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy. DNA damage was detected by the comet assay. Changes in the DNA damage response signaling pathway were analyzed by Western blotting, and apoptosis was detected by flow cytometry.
Results: The expression of TOPK was significantly greater in CRC tissues at grades 2-4 than in those at grade 1. After irradiation, CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins, including phospho-cyclin-dependent kinase 1 (p-CDK1), phospho-ataxia telangiectasia-mutated (p-ATM), poly ADP-ribose polymerase (PARP), and meiotic recombination 11 homolog 1 (MRE11).
Conclusions: TOPK was overexpressed in patients with moderately to poorly differentiated CRC. Moreover, TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.
(© 2024. Huazhong University of Science and Technology.)
Databáze: MEDLINE
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