Cross-Resistance of Acquired Radioresistant Colorectal Cancer Cell Line to gefitinib and regorafenib | ||
| Iranian Journal of Medical Sciences | ||
| مقاله 7، دوره 45، شماره 1، فروردین 2020، صفحه 50-58 اصل مقاله (701.12 K) | ||
| نوع مقاله: Original Article(s) | ||
| شناسه دیجیتال (DOI): 10.30476/ijms.2019.44972 | ||
| نویسندگان | ||
| Saeid Afshar1؛ Abdolazim Sedighi Pashaki2؛ Rezvan Najafi1؛ Safoora Nikzad3؛ Razieh Amini1؛ Nooshin Shabab1؛ Omid Khiabanchian4؛ Hamid Tanzadehpanah1؛ Massoud Saidijam* 1 | ||
| 1Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran | ||
| 2Mahdieh Radiotherapy and Brachytherapy Charitable Center, Hamadan, Iran | ||
| 3Department of Medical Physics, Hamadan University of Medical Sciences, Hamadan, Iran | ||
| 4Medical Laboratory, Besat Hospital, Hamadan, Iran | ||
| چکیده | ||
| 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. | ||
| کلیدواژهها | ||
| Colorectal neoplasms؛ Drug Resistance؛ MicroRNAs؛ Gefitinib؛ Regorafenib | ||
| مراجع | ||
|
| ||
|
آمار تعداد مشاهده مقاله: 7,689 تعداد دریافت فایل اصل مقاله: 4,193 |
||