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Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer.
- Source :
- OncoTargets & Therapy; Mar2019, Vol. 12, p2095-2104, 10p
- Publication Year :
- 2019
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 11786930
- Volume :
- 12
- Database :
- Complementary Index
- Journal :
- OncoTargets & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 135798616
- Full Text :
- https://doi.org/10.2147/OTT.S192923