title: Valproic acid suppresses cervical cancer tumor progression possibly via activating Notch1 signaling and enhances receptor-targeted cancer chemotherapeutic via activating somatostatin receptor type II.
abstract: OBJECTIVE
  We investigated the effects of the anti-epilepsy drug valproic acid (VPA) alone and in combination in treating cervical cancer.
  
  
  METHODS
  VPA was investigated for its effects on cervical cancer Hela cell proliferation and tumor growth via in vitro and in vivo assays.
  
  
  RESULTS
  VPA induce cell growth suppression and cell cycle arrest, with an increase of Notch1 that acts as a tumor suppressor and the change of other tumor-associated genes such as p21, p63 and PCNA. VPA was also found to induce cell morphological change, with an increase of certain cell transformation markers such as snail1, snail2 and N-cadherin. Moreover, VPA could significantly up-regulate somatostatin receptor type II (SSTR2). Our in vivo study further demonstrated that VPA via inducing SSTR2 up-regulation extremely enhanced the anti-tumor ability of the SSTR2-preferential cytotoxic COL-SST conjugate in xenografts.
  
  
  CONCLUSIONS
  VPA could not only suppress tumor progression but also provide a novel promising therapeutic choice in combination with a receptor-targeted cytotoxic conjugate via activating the specific receptor.
authors: Department of Medicine, Peptide Research Laboratories, Tulane Health Sciences Center, New Orleans, LA 70112-2699, USA.
authors: Cheguo
authors: C
authors: Tsai
authors: Juliana S
authors: JS
authors: Leslie
authors: Laura G
authors: LG
authors: Franko-Tobin
authors: Monica C
authors: MC
authors: Prasnal
authors: Tong
authors: T
authors: Yang
authors: L
authors: L
authors: Vienna Mackey
authors: Joseph A
authors: JA
authors: Fuselier
authors: David H
authors: DH
authors: Coy
authors: Mingqiu
authors: M
authors: Liu
authors: Changyuan
authors: C
authors: Yu
authors: Lichun
authors: L
authors: Sun
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000627:therapeutic use; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004338:Drug Combinations; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression; D016158:Genes, p53 / Q000187:drug effects; D006367:HeLa Cells; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013004:Somatostatin / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; C081876:CKAP4 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004338:Drug Combinations; D006728:Hormones; D008565:Membrane Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D017481:Receptors, Somatostatin; D050257:Tubulin Modulators; D013004:Somatostatin; D014635:Valproic Acid; C093733:somatostatin receptor 2; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D003078:Colchicine