1. Molecular Medicine Department, Pasteur Institute of Iran 2. Molecular Medicine Department, Pasteur Institute of Iran 3. Department of Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences
Abstract
Introduction
Schedules containing oxaliplatin plus 5-fluorouracil were demonstrated to enhance an objective response rate more profoundly than 5-fu monotherapy, however acquired chemoresistance mitigate drug effects in over 90% of patients with metastatic colorectal cancer. in this sense, detailed mechanism underlying resistance to oxaliplatin remain of paramount clinical importance to unveil therapeutic strategies aiming to overcome cancer cell drug resistance. the implication of mirnas has been recently found in regulation of drug metabolism and drug efflux. several studies have been emphasized on tumor suppressor properties of mir-302c in many cancers. the current study has been investigated the pharmacokinetics of mir-302c-5p in oxaliplatin resistant sw480 cell line.
Methods
Invitro oxaliplatin resistant colorectal cancer (crc) models as sw480/oxr were developed by intermittent exposure of sw480 colon cancer cells to increasing concentrations of oxaliplatin. expression of mir-302c-5p in sw480 and sw480/oxr cell lines were detected by stem-loop real-time pcr. sw480/oxr were transfected with mir-302c-5p-contained lentiviral vectors. the expression level of abcb1 were assessed by real-time pcr. oxaliplatin sensitivity was analyzed by mtt assay in these cells.
Results
Prediction of the binding between mir-302c-5p and 3-utr of abcb1 mrna was performed by bioinformatics analyses despite abcb1 upregulation, expression of mir-302c-5p was downregulated in oxaliplatin resistant crc cell line sw480/oxr as compared with its parental line sw480. overexpression of mir-302c-5p decreased the expression of abcb1 mrna in sw480/oxr cells and enhanced the sensitivity of resistant cells to oxaliplatin.
Conclusion
Serving as a key contributor of acquired resistance to oxalipalatin, abcb1 was downregulated by mir-302c-5p which sensitize resistant crc cells to oxaliplatin.
Keywords
Colorectal neoplasia, drug resistance, oxaliplatin, abcb1, mir-302c-5p
