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International Journal of Molecular and Cellular Medicine، جلد ۱۰، شماره ۱، صفحات ۲۳-۳۳
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| عنوان فارسی |
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| چکیده فارسی مقاله |
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| کلیدواژه‌های فارسی مقاله |
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| عنوان انگلیسی |
DCLK1 Inhibition Sensitizes Colorectal Cancer Cells to Radiation Treatment |
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| چکیده انگلیسی مقاله |
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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| کلیدواژه‌های انگلیسی مقاله |
DCLK1, ionizing radiation, colorectal cancer, radiosensitivity |
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| نویسندگان مقاله |
| Chiman Mohammadi
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| Ali Mahdavinezhad
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| Massoud Saidijam
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| Fatemeh Bahreini
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| Abdolazim Sedighi Pashaki
Mahdieh Radiotherapy and Brachytherapy Charitable Center, Hamadan, Iran.
| Mohammad Hadi Gholami
Mahdieh Radiotherapy and Brachytherapy Charitable Center, Hamadan, Iran.
| Rezvan Najafi
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
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| نشانی اینترنتی |
http://ijmcmed.org/browse.php?a_code=A-10-942-2&slc_lang=en&sid=1 |
| فایل مقاله |
فایلی برای مقاله ذخیره نشده است |
| کد مقاله (doi) |
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| زبان مقاله منتشر شده |
en |
| موضوعات مقاله منتشر شده |
Cancer |
| نوع مقاله منتشر شده |
Original Article |
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