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  • FAK alleviates radiation_induced rectal injury by decreasing apoptosis.

  • 【作者】Li, Jun-Jun;Tu, Wen-Zhi;Chen, Xu-Ming;Ying, Hou-Yu;Chen, Ying;Ge, Yu-Long;Wang, Jing;Xu, Yi;Chen, Ting-Feng;Zhang, Xiao-Wei;Ye, Jin-Jun;Liu, Yong
  • 【作者单位】1 Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
  • 【出处】Toxicology & Applied Pharmacology
  • 【年份】2018
  • 【卷号】Vol.360
  • 【页码】131-140
  • 【关键词】FAK;Radiosensitivity;Radiotherapy;Rectal injury
  • 【ISSN】0041-008X;1096-0333
  • 【分类号】615.9
  • 【摘要】Radiation-induced rectal injury is closely related with radiotherapy efficiency. Here, we investigated the effect of focal adhesion kinase (FAK) in radiation-induced rectal injury. Peripheral blood samples of patients with rectal cancer were collected prior to radiotherapy. Differentially expressed genes and copy number variations (CNVs) were analyzed by microarray analysis. The CTCAE v3.0 toxicity grades were used to assess acute rectal injury. The radiosensitivity of human intestinal epithelial crypt (HIEC) cells were assayed by colony formation, mitochondrial membrane potential, flow cytometry and western blotting. The rectums of C57BL/6 mice were X-irradiated locally with a single dose of 15 Gy. The effect of FAK on radiation-induced injury was investigated by hematoxylin-eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR). FAK mRNA level was inversely correlated with rectal injury severity in patient samples. A CNV amplification located on chromosome 8 was closely related with FAK. Further functional assays revealed increased levels of γH2AX expression and apoptosis-related proteins in FAK-silenced HIEC cells. The ratio of TUNEL, cl-caspase-3, cyto-c and bax/bcl-2 expression in the rectum mucosa treated with a FAK inhibitor increased significantly. These results demonstrated that FAK reduced radiation-induced rectal injury by decreasing apoptosis. Highlights • FAK mRNA level was inversely correlated with rectal injury severity induced by radiotherapy. • FAK decreased the radiosensitivity of human intestinal epithelial crypt (HIEC) cells. • FAK reduced radiation-induced rectal injury by decreasing apoptosis of HIEC cells.
  • 【文献类型】外文期刊

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