ArticleCurrent medical science2024
TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response.
Article in Current medical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The trial behind it
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Who cites it
4 citing papers in PubMed.
- Review
- The Correlation ofCancers · 2026Article
- The Roles of TOPK in Tumorigenesis and Development: Structure, Mechanisms, Pathways, and Therapeutic Implications.International journal of biological sciences · 2026Review
- [PDZ-binding kinase as a prognostic biomarker for pancreatic cancer: a pan-cancer analysis and validation in pancreatic adenocarcinoma cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAbnormal 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.
methodsThe 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.
resultsThe 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).
conclusionsTOPK 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.
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Registered trials
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