The Study Of Fusobacterium Nucleatum Promotes Cetuximab Resistance In Colorectal Cancer

Background and objective: Fn was overabundance in right-sided CRC patients compared with left-sided CRC patients.KRAS/NRAS/BRAF wild-type patients with left-sided CRC were more beneficial from cetuximab compared to those with right-sided CRC.Failure of drug therapy is the main cause of tumor recurrence and poor clinical prognosis in patients with CRC.Here,we investigated the contribution of Fn to cetuximab resistance.The important role of Fn in the treatment of CRC was expounded,and the theoretical basis was provided for the prevention and treatment of CRC and the development of microbial markers.Methods: Caco2 and HT29 in CRC cells were infected by Fn,and the targeted drug cetuximab was added,the drug resistance of colorectal cancer cells was detected by cell proliferation,cell viability,clone formation and apoptosis.At the same time,a nude mouse model of colorectal cancer transplantation was constructed to further verify the reduced sensitivity of cetuximab after infection with Fn.In terms of mechanism,transcriptome sequencing,cell cycle experiment and western blot experiment were used to elucidate how Fn affected the sensitivity of cetuximab.Results: In vitro and in vivo,Fn promoted the resistance of CRC to cetuximab.Mechanistically,Fn targets Pl3K/AKT and JAK/STAT3 pathways to promote CRC resistance to cetuximab.Conclusion: Through up-regulation of phosphorylated protein AKT and STAT3,Fn leads to continued activation of the downstream EGFR pathway,which promotes resistance of CRC cells to cetuximab.Monitoring and targeting Fn and its related signaling pathways may provide valuable reference for clinical medication and improve the prognosis of CRC patients.