title: Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma.
abstract: Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. amazatou@gmail.com.
authors.forename: Aya
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Mizobuchi
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shono
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Fujihara
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Kageji
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kitazato
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Matsuzaki
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Mure
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kuwayama
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sumi
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Oltea
authors.initials: O
authors.lastname: Sampetrean
authors.affiliation: Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahirao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D000068579:Celecoxib / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology / Q000528:radiation effects; D005910:Glioma / Q000473:pathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism / Q000494:pharmacology; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; C075640:ID3 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D000068579:Celecoxib
keywords: Akt; COX-2; ID3; Low-grade glioma; Survivin