title: Hypoxia-inducible factor-1α protects cervical carcinoma cells from apoptosis induced by radiation via modulation of vascular endothelial growth factor and p53 under hypoxia.
abstract: BACKGROUND
  The aim of the study was to assess the role of irradiation in the expression of HIF-1a, VEGF, and P53 in human cervical carcinoma cells under a simulated hypoxia environment.
  
  
  METHODS
  The tetrazolium-based colorimetric cellular assay (MTT) and flow cytometry (FCM) were used to detect the growth inhibition rates of HeLa cells in different groups. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to observe gene and protein expression of HIF-1α, VEGF, and P53. The effect of HIF-1α on radioresistance and expression of VEGF and P53 were confirmed with the HIF-1α siRNA in vivo and in vitro.
  
  
  RESULTS
  Hypoxic conditions enhanced the radiation resistance dependent on HIF-1α by elevating the expression of VEGF and inhibiting the expression of p53. After transfection of HIF-1α siRNA, MTT assay showed the survival rates were increased in the cells receiving irradiation under hypoxia. The expression of VEGF decreased significantly more than that of cells transfected with sense oligodeoxynucleotides, while an opposite result was found in the expression of P53 protein in the same X-ray dose (p<0.05). In vivo, the radioresistance of HIF-1α was consistent with the results in vitro.
  
  
  CONCLUSIONS
  In the future, we might inhibit human cervical cancer progression and enhance the radiosensitivity by inhibiting HIF-1α to reduce VEGF and increase P53 expression. The challenge is how to use this information to optimize cancer therapy.
authors.affiliation: Department of Radiology, Fuzhou General Hospital, Fuzhou, Fujian, China (mainland).
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Anesthesia, Fuzhou General Hospital, Fuzhou, Fujian, China (mainland).
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Radiology, Fuzhou General Hospital, Fuzhou, Fujian, China (mainland).
authors.forename: Huihua
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, Fuzhou General Hospital, Fuzhou, Fujian, China (mainland).
authors.forename: Fengmei
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014965:X-Rays
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009841:Oligonucleotides; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A