Colorectal cancer (CRC) is one of the most prevalent diagnosed cancers and a common cause of cancer-related mortality. Despite effective clinical responses, a large proportion of patients undergo resistance to radiation therapy. Therefore, the identification of efficient targeted therapy strategies would be beneficial to overcome cancer radioresistance. Doublecortin-like kinase 1 (DCLK1) is an intestinal and pancreatic stem cell marker that showed overexpression in a variety of cancers. The transfection of siRNA to normal HCT-116 cells was performed, and then cells were irradiated with X-rays. The effects of inhibition on cell survival, apoptosis, cell cycle, DNA damage response (ATM and γH2AX proteins), epithelial-mesenchymal transition (EMT) related genes (vimentin, N-cadherin, and E-cadherin), cancer stem cells markers (, , , and ), and β-catenin signaling pathway (β-catenin) were evaluated. siRNA downregulated expression in HCT-116 cells at both mRNA and protein levels (P 0.01). Colony formation assay showed a significantly reduced cell survival in the siRNA transfected group in comparison with the control group following exposure to 4 and 6 Gy doses of irradiation (P <0.01). Moreover, the expression of cancer stem cells markers (P <0.01), EMT related genes (P <0.01), and DNA repair proteins including pATM (P <0.01) and γH2AX (P <0.001) were significantly decreased in the transfected cells in comparison with the nontransfected group after radiation. Finally, the cell apoptosis rate (P <0.01) and the number of cells in the G0/G1 phase in the silencing group was increased (P <0.01). These findings suggest that can be considered a promising therapeutic target for the treatment of radioresistant human CRC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256833 | PMC |
http://dx.doi.org/10.22088/IJMCM.BUMS.10.1.23 | DOI Listing |
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