Quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo

• Published in: Journal of experimental & clinical cancer research 2016-04, Vol.35 (62), p.61-61, Article 61
• Main Authors: Li, Junyang, Tang, Chao, Li, Liwen, Li, Rujun, Fan, Youwu
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Apoptosis; Benzoates - administration & dosage; Benzoates - pharmacology; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Care and treatment; Cell Cycle - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Complications and side effects; Cyclooxygenase 2 - metabolism; Gene Expression Regulation, Neoplastic - drug effects; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma multiforme; Heat shock proteins; HSP27 Heat-Shock Proteins - metabolism; Humans; Inflammation; Influence; Mice; Quercetin - administration & dosage; Quercetin - pharmacology; Risk factors; Urea - administration & dosage; Urea - analogs & derivatives; Urea - pharmacology; Xenograft Model Antitumor Assays
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-016-0331-1

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. 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. 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. These results indicate that combination of t-AUCB and quercetin may be a potential approach to treating glioblastoma.