title: Quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo.
abstract: BACKGROUND
  Evidences indicate that inflammatory process plays pivotal role in tumor disease. Soluble epoxide hydrolase inhibitors (sEHIs) have been shown to participate in anti-inflammation and tumorigenesis by protecting epoxyeicosatrienoic acids (EETs). Although we have previously revealed some effects of t-AUCB on glioma in vitro, further investigations are needed to demonstrate its effects on glioblastoma growth in vivo and how to strengthen its antitumor effect.
  
  
  METHODS
  CCK-8 kit was used to test cell growth. Cell migration capacity was performed by wound healing assays. Transwell assay was used to test cell invasion potency. Cell-cycle analysis and cell apoptosis was performed by flow cytometry. The activity of caspase-3 in cells was measured using caspase-3 activity assay kits. Total RNA was extracted from cells lysated by TRIzol reagent. qRT-PCR was performed by ABI 7500 fast RT- PCR system. Lipofectamine RNAiMAX Transfection Reagent (Invitrogen) was used for siRNA transfection. Western blootting was used to test protein expression. Tumor cell xenograft mouse models were used for in vivo study. The SPSS version 17.0 software was applied for statistical analysis.
  
  
  RESULTS
  Our data shown that t-AUCB inhibits cell proliferation, migration and invasion and induces cell cycle G1 phase arrest in vitro but induces no cell apoptosis; increased Hsp27 activation and following COX-2 overexpression confer resistance to t-AUCB treatment in glioblastoma both in vitro and in vivo; quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo.
  
  
  CONCLUSIONS
  These results indicate that combination of t-AUCB and quercetin may be a potential approach to treating glioblastoma.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing City, 210002, Jiangsu Province, China. ljy_njmu@126.com.
authors.forename: Junyang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing City, 210002, Jiangsu Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing City, 210002, Jiangsu Province, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.
authors.forename: Rujun
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing City, 210002, Jiangsu Province, China. fanyouwu_njzy@126.com.
authors.forename: Youwu
authors.initials: Y
authors.lastname: Fan
mesh_terms: D000818:Animals; D001565:Benzoates / Q000008:administration & dosage* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones; D011794:Quercetin / Q000008:administration & dosage* / Q000494:pharmacology; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: C524106:4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid; D001565:Benzoates; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D014508:Urea; D011794:Quercetin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Cyclooxygenase 2; Glioma; Heat shock protein 27; Inhibitor; Soluble epoxide hydrolase