title: The role and mechanisms of nanoparticles to enhance radiosensitivity in hepatocellular cell.
abstract: OBJECTIVE
  This work aimed to investigate whether nanosilver and nanogold could modulate irradiation response of hepatocellular carcinoma cells (HepG2) in vitro and the underlying mechanisms.
  
  
  METHODS
  Cell viability of the HCC cell lines (HepG2) was examined by the 3-(4,5-dimethylthiazol-yl)-5(3-carboxymethoxyphenyl)-2H-terazolium (MTT) assays. Clonogenic growth assays of HepG2 were determined by colony formation assays. Cell apoptosis and cell cycle distribution changes were analyzed by flow cytometry (FCM). DNA damage was assessed by monitoring γ-H2AX foci in irradiated cells with immunofluorescence microscopy. The expression of regulating molecules was analyzed by using western blotting for Bax, caspase-3, and Bcl-2, and the content of catalase (Catalase CAT), superoxide dismutase (SOD), glutathione (Total of GSH) were determined.
  
  
  RESULTS
  Our results show that nanosilver and nanogold reduced the viability of HepG2 cells. Nanosilver and nanogold significantly enhanced the radiosensitivity of HepG2 cells. Obtained by Dq, the SER of 1/5 silver+irradiation group, 1/10 silver+irradiation group, 1/5 gold+irradiation group, 1/10 gold+irradiation group, respectively, were 1.977, 1.823, 1.762, 1.597. Immunofluorescence assays showed that there was 32.2±1.2% of irradiated HepG2. And 48.1±0.1% of 1/5 IC50 nanogold+6Gy group, 43.7±0.8% of 1/10 IC50 nanogold+6Gy group, 48.8±1.2% of 1/5 IC50 nanosilver+6Gy group,41.5±1.5% of 1/10 IC50 nanosilver+6Gy group. Nanosilver and nanogold could upregulate the expression of Bax, caspase-3 and downregulate the expression of Bcl-2. Moreover, the content of CAT, SOD and Total GSH were significantly reduced.
  
  
  CONCLUSIONS
  Nanosilver and nanogold could enhance the radiationsensitivity of hepatocellular carcinoma cells. Elevated DNA damage levels and apoptosis may be responsible for this.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Department of Oncology, The Second Affiliated Hospital of Southeast University, Nanjing 210003, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zheng
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Juan
authors.initials: J
authors.lastname: Wei
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Tong
authors.forename: Yong-Qian
authors.initials: YQ
authors.lastname: Shu
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D006046:Gold / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D011839:Radiation, Ionizing; D012834:Silver / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D012834:Silver; D006046:Gold; D053148:Caspase 3
keywords: Apoptosis; HepG2 cells; Nanogold; Nanosilver; Radiosensitivity; γ-H2AX