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Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer
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 foun...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430989/ https://www.ncbi.nlm.nih.gov/pubmed/30936724 http://dx.doi.org/10.2147/OTT.S192923 |
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author | Liu, Zhuo Yu, Miao Fei, Bingyuan Sun, Jing Wang, Dongxin |
author_facet | Liu, Zhuo Yu, Miao Fei, Bingyuan Sun, Jing Wang, Dongxin |
author_sort | Liu, Zhuo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6430989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64309892019-04-01 Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer Liu, Zhuo Yu, Miao Fei, Bingyuan Sun, Jing Wang, Dongxin Onco Targets Ther Original Research 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. Dove Medical Press 2019-03-20 /pmc/articles/PMC6430989/ /pubmed/30936724 http://dx.doi.org/10.2147/OTT.S192923 Text en © 2019 Liu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Liu, Zhuo Yu, Miao Fei, Bingyuan Sun, Jing Wang, Dongxin Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer |
title | Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer |
title_full | Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer |
title_fullStr | Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer |
title_full_unstemmed | Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer |
title_short | Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer |
title_sort | nonhomologous end joining key factor xlf enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430989/ https://www.ncbi.nlm.nih.gov/pubmed/30936724 http://dx.doi.org/10.2147/OTT.S192923 |
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