title: In Vitro and In Vivo Radiosensitizing Effect of Valproic Acid on Fractionated Irradiation.
abstract: OBJECTIVE
  This study was conducted in order to validate the radiosensitization effect of valproic acid, a biologically available histone deacetylase inhibitor, for fractionated radiation.
  
  
  METHODS
  Radiosensitization effect of valproic acid was tested for the A549 cell line and U87MG cell line in vitro. Fractionated irradiation of 12 Gy in four fractions was administered on D2-5 with valproic acid, 150 mg/Kg, ip, bid for six consecutive days (D1-6) to A549 and U87MG tumors implanted in BALB/c-nude mice. A growth delay curve was formulated.
  
  
  RESULTS
  Radiosensitization effect of valproic acid was found for both cell lines; A549 at 1.5 mM and 3.0 mM concentration and U87MG at 3.0 mM concentration. In growth delay analysis, a statistically significant radiosensitization effect was observed for both tumors (p < 0.001 for both tumors). Difference for change in slope for control and valproic acid versus radiotherapy and radiotherapy plus valproic acid showed borderline significance for the U87MG cell line (p=0.065), indicating beyond additive effect, whereas this difference was statistically insignificant for A549 tumor (p=0.951), indicating additive effect.
  
  
  CONCLUSIONS
  Results of this study indicate that a radiosensitizing effect for fractionated radiotherapy of valproic acid for A549 and U87MG tumors in vivo is evident and that it may be more than additive for U87MG tumors. Further exploitation of histone deacetylase inhibitors in clinical trials is warranted.
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.|Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Eui Kyu
authors.initials: EK
authors.lastname: Chie
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.|Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.|Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Hak Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.|Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.|Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.|Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Il Han
authors.initials: IH
authors.lastname: Kim
keywords: Glioblastoma; Non-small-cell lung carcinoma; Radiation; Radiation tolerance; Valproic acid