COX-2/sEH dual inhibitor PTUPB suppresses glioblastoma growth by targeting epidermal growth factor receptor and hyaluronan mediated motility receptor

AIMS: Cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) dual inhibitor, PTUPB, has been demonstrated to inhibit angiogenesis, primary tumor growth and metastasis. The aim of this study is to investigate the effects of PTUPB on glioblastoma cells and xenograft model. RESULTS: We show here that PTUPB inhibits glioblastoma cell proliferation and G1 phase cell cycle arrest in vitro, and suppresses the tumor growth and angiogenesis in vivo. The expression and activation of epidermal growth factor receptor (EGFR) and its downstream kinases, ERK1/2 and AKT, are reduced by PTUPB, indicating that the EGF/EGFR signaling pathway is a potential target. Moreover, PTUPB dramatically suppresses expression of hyaluronan mediated motility receptor (HMMR) in the glioblastoma cell lines and xenograft mouse model, suggesting that the HMMR is the other potential target. MATERIALS AND METHODS: Cellular immunofluorescence assays were used for cell staining of actin fibers and HMMR. CCK-8 kit was used for cell proliferation assay. Cell-cycle analysis was performed by flow cytometry. Quantitative real-time PCR assay was performed to test mRNA level. Western blot analysis was used to test protein expression. Immunohistochemical staining assay was used for xenograft tumor tissue staining of Ki-67, CD31 and HMMR. The SPSS version 17.0 software was applied for statistical analysis. CONCLUSIONS: Our data demonstrate that PTUPB is a potential therapeutic agent to treat glioblastomas.