title: Deficiency of 53BP1 inhibits the radiosensitivity of colorectal cancer.
abstract: The present study aimed to observe the influence of p53 binding protein 1 (53BP1) silencing on the radiosensitivity of colorectal cancer (CRC) cells and investigated the potential underlying mechanisms. The differences in radiosensitivity among four CRC cells were detected by the clone formation assay, while the expression of their 53BP1 was detected by the western blot analysis. HCT116 cells with relatively high expression of 53BP1 were selected to silence the expression of 53BP1 by shRNA intervention. The influence on proliferation, apoptosis, and cell cycle distribution was detected by immunofluorescent staining of Ki-67 and flow cytometry. The expression of relevant proteins in the apoptotic pathway ATM-CHK2-p53 was further analyzed by western blot analysis. The expression of 53BP1 was found to be closely related to the radiosensitivity of the CRC cells. Decreased expression of 53BP1 led to the tolerance of HCT116 cells to radiation. The detection of tumor proliferation, apoptosis, and cell cycle showed that decreased expression of 53BP1 resulted in an increased S-phase percentage of HCT116 cells, an increased proliferating rate, and a decreased apoptotic rate after radiation. The analysis of the molecular pathway showed that the reduced expression of 53BP1 decreased the protein expression of ATM, CHK2, and the phosphorylated products associated with the p53 apoptotic pathway. In conclusion, decreased expression of 53BP1 leads to radiotolerance of CRC cells, and the underlying mechanism is probably related to the decreased expression of relevant proteins in the ATM-CHK2-p53 pathway, which affects cell cycle, apoptosis and proliferation.
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors: Yong
authors: Y
authors: Xiao
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors: Xiumei
authors: X
authors: Zheng
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors: Ai
authors: A
authors: Huang
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors: Tao
authors: T
authors: Liu
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors: Tao
authors: T
authors: Zhang
authors: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors: Hong
authors: H
authors: Ma
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D005260:Female; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000172:deficiency*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1