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

作　　者：Shi-gui PANG Xin ZHANG Zhao-xin LI Li-fei HE Feng CHEN Ming-long LIU Ying-ze HUANG Jian-mei MO Kong-lan LUO Juan-juan XIAO Feng ZHU 

机构地区：[1]Department of Oncology,The Affiliated Hospital of Guilin Medical University,Guilin,541001,China [2]Cancer Research Institute,The Affiliated Hospital of Guilin Medical University,Guilin,541001,China [3]Translational Medical Center,Huaihe Hospital,Henan University,Kaifeng,475000,China [4]Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair,The Affiliated Hospital of Guilin Medical University,Guilin,541001,China

出　　处：《Current Medical Science》2024年第3期545-553,共9页当代医学科学（英文）

基　　金：supported by the Guangxi Zhuang Autonomous Region Program of China(No.Z-C20220797);Guangxi Science and Technology Planning Project of China(No.Guike AD20297047);National Natural Science Foundation of China(No.81902849).

摘　　要：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.

关 键 词：T-lymphokine-activated killer cell-originated protein kinase colorectal cancer DNA damage response RADIOSENSITIVITY 

分 类 号：R735.3[医药卫生—肿瘤]