TY - JOUR ID - 44972 TI - Cross-Resistance of Acquired Radioresistant Colorectal Cancer Cell Line to gefitinib and regorafenib JO - Iranian Journal of Medical Sciences JA - IJMS LA - en SN - 0253-0716 AU - Afshar, Saeid AU - Sedighi Pashaki, Abdolazim AU - Najafi, Rezvan AU - Nikzad, Safoora AU - Amini, Razieh AU - Shabab, Nooshin AU - Khiabanchian, Omid AU - Tanzadehpanah, Hamid AU - Saidijam, Massoud AD - Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran AD - Mahdieh Radiotherapy and Brachytherapy Charitable Center, Hamadan, Iran AD - Department of Medical Physics, Hamadan University of Medical Sciences, Hamadan, Iran AD - Medical Laboratory, Besat Hospital, Hamadan, Iran Y1 - 2020 PY - 2020 VL - 45 IS - 1 SP - 50 EP - 58 KW - Colorectal neoplasms KW - Drug Resistance KW - MicroRNAs KW - Gefitinib KW - Regorafenib DO - 10.30476/ijms.2019.44972 N2 - Background: Usually, chemoradiotherapy can be used for the treatment of locally advanced colorectal cancer (CRC) before surgery. On the other hand, some studies have shown that fractional radiation of tumor cells leads to chemoresistance. The aim of this study was to evaluate the chemoresistance of radioresistant sub-line (RR sub-line).Methods: This study was done in Hamadan University of Medical Sciences in 2017-2018. MTT assay and sub-G1 fraction analysis by flow cytometry were used to evaluate cross-resistance of RR sub-line to gefitinib and regorafenib. Real-time PCR was used to investigate the role of four miRNAs and their target genes in the cross-resistance of RR sub-line. The t test and repeated measures test were used for the assessment of statistical significance between groups.Results: The IC50 of gefitinib and regorafenib for RR sub-line were significantly higher than those of the parental cell line. On the other hand, the resistance index of RR sub-line for gefitinib and regorafenib were 1.92 and 1.44, respectively. The sub-G1 fraction of RR sub-line following treatment with gefitinib and regorafenib was significantly lower than that of the parental cell line (P=0.012 and P=0.038, respectively). The expression of miR-9, Let-7e, and Let-7b in RRsub-line was significantly lower than that of the parental cell line. However, NRAS, IGF1R, NFKB1, and CCND1 found to be upregulated in RR sub-line in comparison with the parental cell line.Conclusion: We can conclude that the acquired RR sub-line was cross-resistance to gefitinib and regorafenib. Furthermore, miR-9/NFKB1, let-7b/CCND1, let-7e/NRAS, and IGF1R played essential roles in the chemoradioresistance of CRC. UR - https://ijms.sums.ac.ir/article_44972.html L1 - https://ijms.sums.ac.ir/article_44972_b8b7095573e2d6ef457ee92c488f75e1.pdf ER -