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DCLK1 Inhibition Sensitizes Colorectal Cancer Cells to Radiation Treatment
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Chiman Mohammadi1    , Ali Mahdavinezhad1 , Massoud Saidijam1 , Fatemeh Bahreini1 , Abdolazim Sedighi Pashaki2 , Mohammad Hadi Gholami2 , Rezvan Najafi 3 |
1- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
2- Mahdieh Radiotherapy and Brachytherapy Charitable Center, Hamadan, Iran.
3- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. , najafi2535@gmail.com |
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Abstract: (4367 Views) |
| 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. DCLK1siRNA 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. |
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| Keywords: DCLK1, ionizing radiation, colorectal cancer, radiosensitivity |
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Full-Text [PDF 740 kb]
(1183 Downloads)
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Type of Study: Original Article |
Subject:
Cancer
Received: 2020/12/16 | Accepted: 2021/02/27 | Published: 2021/01/21
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