title: Enhancement of radiosensitivity in human esophageal carcinoma cells by fenofibrate and its potential mechanism.
abstract: OBJECTIVE
  Fenofibrate is a specific agonist of PPARα, and is characterized by relatively low systemic toxicity. Recent studies have revealed that fenofibrate suppresses the growth of several cancer lines in vitro, but the exact relation between fenofibrate and irradiation has not been explored. The purpose of this study was to investigate the radiosensitivity enhancement effects of fenofibrate combined with radiation on the human esophageal carcinoma cell lines Eca-109 and TE1, and the potential mechanism underlying these effects.
  
  
  METHODS
  The Eca-109 and TE1 cell lines were tested by the CCK-8 assay for cell proliferation. The multitarget click model was used to delineate the survival curve and radiosensitivity was determined after cells were treated with fenofibrate and/or x-ray radiation. Flow cytometry was used to examine the effect of fenofibrate and radiation on the cell cycle. The expression of vascular endothelial growth factor (VEGF) protein was detected by Western blot analysis.
  
  
  RESULTS
  When given alone, fenofibrate had a time- and concentration-dependent cytotoxic effect on cells. The dose-enhancement ratio for combined fenofibrate and radiation increased markedly compared with fenofibrate alone. Further, the ratio of cells in the G2/M phase after fenofibrate and radiation was higher than that after fenofibrate or irradiation alone. The expression of VEGF protein was suppressed after treatment with fenofibrate alone or fenofibrate plus radiation.
  
  
  CONCLUSIONS
  Fenofibrate can enhance the radiosensitivity of human esophageal carcinoma cells by increasing G2/M phase arrest. Modulation of VEGF expression could contribute in vivo to a favorable interaction.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Li
authors.forename: Jun-Dong
authors.initials: JD
authors.lastname: Zhou
authors.forename: Shi-Tao
authors.initials: ST
authors.lastname: Zou
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Xin-Jun
authors.initials: XJ
authors.lastname: Meng
authors.forename: Jin-Chang
authors.initials: JC
authors.lastname: Wu
mesh_terms: D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival; D004307:Dose-Response Relationship, Radiation; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011345:Fenofibrate / Q000494:pharmacology*; D005434:Flow Cytometry; D016195:G2 Phase; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D011838:Radiation-Sensitizing Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011345:Fenofibrate