dclk1 inhibition sensitizes colorectal cancer cells to radiation treatment

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 dclk1 sirna to normal hct-116 cells was performed, and then cells were irradiated with x-rays. the effects of dclk1 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 (cd44, cd133, aldh1, and bmi1), and β‐catenin signaling pathway (β‐catenin) were evaluated. dclk1 sirna downregulated dclk1 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 dclk1 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 dclk1 group was increased (p <0.01). these findings suggest that dclk1 can be considered a promising therapeutic target for the treatment of radioresistant human crc.