cross-resistance of acquired radioresistant colorectal cancer cell line to gefitinib and regorafenib

Background: usually, chemoradiotherapy can be used for thetreatment of locally advanced colorectal cancer (crc) beforesurgery. on the other hand, some studies have shown thatfractional radiation of tumor cells leads to chemoresistance.the aim of this study was to evaluate the chemoresistance ofradioresistant sub-line (rr sub-line).methods: this study was done in hamadan university ofmedical sciences in 2017-2018. mtt assay and sub-g1fraction analysis by flow cytometry were used to evaluate crossresistanceof rr sub-line to gefitinib and regorafenib. real-timepcr was used to investigate the role of four mirnas and theirtarget genes in the cross-resistance of rr sub-line. the t test andrepeated measures test were used for the assessment of statisticalsignificance between groups.results: the ic50 of gefitinib and regorafenib for rr sub-linewere significantly higher than those of the parental cell line. onthe other hand, the resistance index of rr sub-line for gefitiniband regorafenib were 1.92 and 1.44, respectively. the sub-g1fraction of rr sub-line following treatment with gefitinib andregorafenib was significantly lower than that of the parentalcell line (p=0.012 and p=0.038, respectively). the expressionof mir-9, let-7e, and let-7b in rrsub-line was significantlylower than that of the parental cell line. however, nras,igf1r, nfkb1, and ccnd1 found to be upregulated in rrsub-line in comparison with the parental cell line.conclusion: we can conclude that the acquired rr sub-linewas cross-resistance to gefitinib and regorafenib. furthermore,mir-9/nfkb1, let-7b/ccnd1, let-7e/nras, and igf1rplayed essential roles in the chemoradioresistance of crc.