The Impact of Nrf2 Silencing on Nrf2-PD-L1 Axis to Overcome OxaliplatinResistance and Migration in Colon Cancer Cells

Background: nuclear factor-erythroid 2-related factor 2 (nrf2) plays a key role inpromoting chemoresistance in various cancers. pd-l1 is one of the downstream targetsof the nrf2 signaling pathway. this molecule has some beneficial impacts on tumorsgrowth by inhibition of the immune system. this study aimed to investigate thepotential role of the nrf2-pd-l1 axis in the promotion of oxaliplatin resistance in coloncancer cells.methods: we examined nrf2, pd- l1, and cd80 expression in the tumor and margintissue samples from crc patients. after that role of the nrf2-pd-l1 axis in promotionof oxaliplatin resistance was investigated.results: our data revealed that nrf2 and pd-l1 mrna expressions were markedlyhigher in tumor tissues compared to margin tissues. the pd-l1 mrna expression levelwas also increased in the resistant cells. however, nrf2 expression was decreased insw480/res cells and increased in ls174t/res cells. the inhibition of nrf2 through sirnatreatment in sw480/res and ls174t/res cells has decreased the ic50 values of oxaliplatin.inhibition of the nrf2 has significantly increased the oxaliplatin-induced apoptosis,and reduced the migration in sw480/res cells.conclusion: it is suggested that effective inhibition of nrf2-pd-l1 signaling pathwayscan be considered as a novel approach to improve oxaliplatin efficacy in colon cancerpatients.