Cyclooxygenase-2 inhibitors induce anoikis in osteosarcoma via PI3K/Akt pathway.

Bing Liu, Liyan Qu, Zhengming Yang, Huimin Tao

Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, PR China.

Medical hypotheses 2012 Jul

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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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Bing Liu, Liyan Qu, Zhengming Yang, Huimin Tao. Cyclooxygenase-2 inhibitors induce anoikis in osteosarcoma via PI3K/Akt pathway. Medical hypotheses. 2012 Jul;79(1):98-100