title: Cyclooxygenase-2 inhibitors induce anoikis in osteosarcoma via PI3K/Akt pathway.
abstract: COX-2, an inducible enzyme, is associated with inflammatory diseases and carcinogenesis. Overexpression of COX-2 occurs in many human malignancies, including osteosarcoma. In our study, we reported that Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt. PI3K/Akt plays an essential role in the cell/extracellar matrix (ECM) and cell/cell adhesion. We hypothesize that COX-2 inhibitors induce anoikis in osteosarcoma via PI3K/Akt, resulted in lack of correct attachment and the down-regulations of β-catenin, TrkB and E-cadherin, which play an essential role in the cell/extracellar matrix (ECM) and cell/cell adhesion. Meanwhile, apoptosis also be disclosed, such as DNA fragments and apoptotic bodies, activation of caspase-8, 9 and cleavage of PARP. With wortmannin, a specific PI3K inhibitor can simulate the effect of COX-2 inhibitors. If our hypothesis is correct, COX-2 inhibitors could cut down the occurrence of metastasis and facilitate the patient who may benefit from addition of COX-2 inhibitors to standard cytotoxic therapy.
authors.affiliation: Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Liyan
authors.initials: L
authors.lastname: Qu
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Yang
authors.forename: Huimin
authors.initials: H
authors.lastname: Tao
mesh_terms: D023102:Anoikis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D006801:Humans; D008962:Models, Theoretical; D012516:Osteosarcoma / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt