title: Valproic acid inhibits the angiogenic potential of cervical cancer cells via HIF-1α/VEGF signals.
abstract: OBJECTIVE
  Cervical cancer is one of the most prevalent malignancies in women worldwide. Therefore, the investigation about the molecular pathogenesis and related therapy targets of cervical cancer is an emergency. The objective of the present study is to investigate the effects of valproic acid (VPA), a histone deacetylase inhibitor, on the angiogenesis of cervical cancer.
  
  
  METHODS
  The effects and mechanisms of VPA on in vitro angiogenesis and vascular endothelial growth factor (VEGF) expression of human cervical cancer HeLa and SiHa cells were investigated.
  
  
  RESULTS
  Our present study reveals that 1 mM VPA can significantly inhibit the in vitro angiogenic potential and VEGF expression of human cervical cancer HeLa and SiHa cells. Further, the transcription and protein levels of hypoxia inducible factor-1α (HIF-1α), and not HIF-1β, are significantly inhibited in VPA-treated cervical cancer cells. Over expression of HIF-1α can obviously reverse VPA-induced VEGF down regulation. VPA-treatment decreases the activation of Akt and ERK1/2 in both HeLa and SiHa cells in a time-dependent manner. The inhibitor of Akt (LY 294002) or ERK1/2 (PD98059) can inhibit VEGF alone and cooperatively reinforce the suppression effects of VPA on HIF-1α and VEGF expression.
  
  
  CONCLUSIONS
  Collectively, our data reveal that the inhibition of PI3K/Akt and ERK1/2 signals are involved in VPA-induced HIF-1α and VEGF suppression of cervical cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Liaocheng Second People's Hospital, Liaocheng, 252600, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Liaocheng People's Hospital, No. 45, Huashan Road, Development Area, Liaocheng, Shandong, 252000, China. youweizhilc@126.com.
authors.forename: W
authors.initials: W
authors.lastname: You
authors.affiliation: Department of Obstetrics and Gynecology, Liaocheng Third People's Hospital, Liaocheng, 252000, China.
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Liaocheng Second People's Hospital, Liaocheng, 252600, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Central Laboratory, Liaocheng People's Hospital, Liaocheng, 252000, China.
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.affiliation: Central Laboratory, Liaocheng People's Hospital, Liaocheng, 252000, China.
authors.forename: R
authors.initials: R
authors.lastname: Du
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D014635:Valproic Acid / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014635:Valproic Acid
keywords: Angiogenesis; Cervical cancer; HIF-1α; VEGF; Valproic acid