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
Conclusion
Our research first demonstrates that the NHEJ pathway, especially its key factor XLF, significantly contributes to chemoresistance in CRC.
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.