title: NU7441 Enhances the Radiosensitivity of Liver Cancer Cells.
abstract: OBJECTIVE
  Radiation therapy, one of the major treatments for liver cancer, causes DNA damage and cell death. Since the liver cancer cells have a strong capacity to repair irradiative injury, new medicines to enhance this treatment are urgently required. In this study, we investigated the effect of NU7441, a synthetic small-molecule compound, as a specific inhibitor of DNA-dependent protein kinase (DNA-PK) in radiosensitization of hepatocellular carcinoma HepG2 cells.
  
  
  METHODS
  Cell Counting Kit-8 (CCK-8) was first used to evaluate the proliferation of HepG2 cells under NU7441 treatment. SDS-PAGE and Western blot were then performed to study the protein expression leading to the DNA damage repair. Further, neutral single cell gel electrophoresis and immunofluorescence assay were carried out to assess DNA repair. Finally, flow cytometry was implemented to examine the changes in cell cycle.
  
  
  RESULTS
  NU7441 reduced the CCK-8 counts in the HepG2 culture, further enhanced 60Cox03B3; radiation injury to HepG2 cells, which was manifested by decreasing the DNA-PKcs (S2056) protein expression, increasing x03B3;H2AX foci number, prolonging the tail moment of the comet cells, and inducing cell cycle arrest at G2/M phase.
  
  
  CONCLUSIONS
  NU7441 inhibited the growth of liver cancer cells, enhanced the radiosensitization of these cancer cells by interfering with the DNA repair and cell cycle checkpoint. These data implicate NU7441 as a potential radiotherapy sensitizer for the treatment of liver cancer.
authors.forename: Chuanjie
authors.initials: C
authors.lastname: Yang
authors.forename: Quanxu
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Liu
authors.forename: Xiulian
authors.initials: X
authors.lastname: Cheng
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jiang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Feng
authors.forename: Pingkun
authors.initials: P
authors.lastname: Zhou
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology* / Q000633:toxicity; D003037:Cobalt Radioisotopes / Q000737:chemistry; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology* / Q000633:toxicity; D011836:Radiation Tolerance / Q000187:drug effects*; D011839:Radiation, Ionizing
chemical_list: C499693:8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one; D002867:Chromones; D003037:Cobalt Radioisotopes; C468783:H2AX protein, human; D006657:Histones; D009025:Morpholines; D051747:DNA-Activated Protein Kinase