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Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer

Authors Liu Z, Yu M, Fei B, Sun J, Wang D

Received 31 October 2018

Accepted for publication 16 January 2019

Published 20 March 2019 Volume 2019:12 Pages 2095—2104

DOI https://doi.org/10.2147/OTT.S192923

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Zhuo Liu,1 Miao Yu,1 Bingyuan Fei,1 Jing Sun,2 Dongxin Wang3

1Department of Gastrointestinal Colorectal and Anal Surgery, China–Japan Union Hospital of Jilin University, Changchun, Jilin 130021, China; 2Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20052, USA; 3Department of Anesthesiology, Jilin Cancer Hospital, Changchun, Jilin 130021, China

Background: Colorectal cancer (CRC) is the third commonly diagnosed cancer with a high risk of death. After curative surgery, 40% of patients will have metastases or develop recurrence. Therefore, chemotherapy is significantly responsible as the major therapy method. However, chemoresistance is found in almost all metastatic patients and remains a critical obstacle to curing CRC.
Materials and methods: Cell viability is analyzed by sulforhodamine B staining assay. The nonhomologous end joining (NHEJ) repair ability of each cell line was determined by NHEJ reporter assay. mRNA expression levels of NHEJ factors are detected by real-time quantitative polymerase chain reaction. The protein expression levels were observed by western blot assay.
Results: Our study found that 5-florouracil (5-Fu) and oxaliplatin (OXA)-resistant HCT116 and LS174T cells showed upregulated efficiency of DNA double-strand repair pathway NHEJ. We then identified that the NHEJ key factor XLF is responsible for the chemoresistance and XLF deficiency sensitizes CRC cells to 5-Fu and OXA significantly.
Conclusion: Our research first demonstrates that the NHEJ pathway, especially its key factor XLF, significantly contributes to chemoresistance in CRC.

Keywords: XLF, nonhomologous end joining, 5-florouracil, oxaliplatin, chemoresistance, colorectal cancer
 

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