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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]

Colorectal cancer (CRC) has been the third commonest cancer in the world. The prognosis of patients with CRC is related to the molecular subtypes and gene mutations, which is prone to recurrence, metastasis, and drug resistance. Mesenchymal stem cells (MSCs) are a group of progenitor ones with the capabilities of self-renewal， multi-directional differentiation, and tissue re-population, which could be isolated from various kinds of tissues and be differentiated into diverse cell types. In recent years, MSCs are applied for mechanisms study of tissue repairing, graft-versus-host disease (GVHD) and autoimmune-related disease, and tumor development, with the advantages of anti‐inflammation, multi-lineage differentiation, and homing capability. Integrating the chemotherapy and MSCs therapy might provide a novel treatment approach for CRC patients. In this review, we summarize the current progress in the integrated treatment of integrating the MSCs and chemotherapy for CRC. [Display omitted] • MSCs process tumor homing and immunomodulatory properties, providing new ideas for the anti-cancer therapies. • MSCs and their exosomes have shown the therapeutic roles in CRC. • Chemotherapeutic drugs and genes can be carried by MSCs to reduce the toxicity for CRC therapy. • The combination of MSCs and chemotherapy can decrease the drug resistance. [ABSTRACT FROM AUTHOR]