title: The effects of a picosecond pulsed electric field on angiogenesis in the cervical cancer xenograft models.
abstract: OBJECTIVE
  The application of picosecond pulsed electric field (psPEF) is a new biomedical engineering technique used in cancer therapy. However, its effects on cervical cancer angiogenesis are not clear. Therefore, the aim of the present study is to investigate the effects of psPEF on angiogenesis in cervical cancer xenograft models.
  
  
  METHODS
  Xenograft tumors were created by subcutaneously inoculating nude mice (athymic BALB/c nu/nu mice) with HeLa cells, then were placed closely between tweezer-type plate electrodes and subjected to psPEF with a gradually increased electric field intensity (0kV/cm, 50kV/cm, 60kV/cm, 70kV/cm). The direct effect on tumor tissue was observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). The changes of blood vessels and oxygen saturation (sO2) of tumors were monitored in vivo by photoacoustic tomography (PAT). The microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factors (HIF-1α and HIF-2α) were detected by immunohistochemical technique (IHC). Their protein expressions and gene transcription levels were evaluated using western blot (WB) and quantitative reverse transcription and polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  PsPEF induced obvious necrosis of cervical cancer tissue; with the increasing of electric field intensity, the MVD, vascular PA signal and sO2 values declined significantly. The protein expression and gene transcription levels of VEGF, HIF1α and HIF2α were significantly decreased at the same time.
  
  
  CONCLUSIONS
  PsPEF exhibited dramatic anti-tumor and anti-angiogenesis effects in cervical cancer xenograft models by exerting direct effect on cancer cells and vascular endothelial cells and indirect effect on tumor angiogenesis-related factors.
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, PR China.
authors: Limei
authors: L
authors: Wu
authors: State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, 400030 Chongqing, PR China.
authors: Chenguo
authors: C
authors: Yao
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, PR China.
authors: Zhengai
authors: Z
authors: Xiong
authors: State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, 400030 Chongqing, PR China.
authors: Ruizhe
authors: R
authors: Zhang
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, PR China.
authors: Zhiliang
authors: Z
authors: Wang
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, PR China.
authors: Yutong
authors: Y
authors: Wu
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, PR China.
authors: Qin
authors: Q
authors: Qin
authors: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, 400010 Chongqing, PR China. Electronic address: huayuanyuan1022@hotmail.com.
authors: Yuanyuan
authors: Y
authors: Hua
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D004560:Electricity; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000628:therapy*; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human
keywords: Hypoxia inducible factor; Photoacoustic imaging; Picosecond pulsed electric field; Uterine cervical neoplasms