Premium
Celecoxib, a cyclooxygenase‐2 inhibitor, induces apoptosis in human osteosarcoma cell line MG‐63 via down‐regulation of PI3K/Akt
Author(s) -
Liu Bing,
Shi Zhongli,
Feng Jie,
Tao Huimin
Publication year - 2008
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2007.10.008
Subject(s) - survivin , celecoxib , pi3k/akt/mtor pathway , apoptosis , wortmannin , protein kinase b , cisplatin , chemistry , cancer research , cyclooxygenase , pharmacology , biology , medicine , biochemistry , chemotherapy , enzyme
Cyclooxygenase‐2 (COX‐2), involved in the inhibition of apoptosis and, the potentiation of cell growth, is frequently overexpressed in human malignancies including osteosarcoma (OS). We have attempted to identify the anti‐proliferation of celecoxib, a selective COX‐2 inhibitor, and the combination of celecoxib and cisplatin in MG‐63 cells, and to explore the potential molecular mechanisms involved. MG‐63 cells were treated with the combination of celecoxib and cisplatin or either agent alone for 48 h in serum‐supplemented medium. Celecoxib caused G1 phase arrest and significantly inhibited cell growth, as well as potentiating cisplatin‐induced apoptosis. The effect was dose‐dependent, and apoptotic changes such as DNA fragments and apoptotic bodies were observed. However, downregulation of COX‐2 did not occur in cells treated with celecoxib. Phosphoinositide‐3‐kinase (PI3K)/Akt, survivin, bcl‐2 were significantly downregulated in cells treated with the combination of celecoxib and cisplatin, and decreased survivin and bcl‐2 levels were found in cells with wortmannin, a specific PI3K inhibitor. Moreover, the decreased expressions of procaspase‐9, procaspase‐3 and cleaved PARP‐1 were detected by Western blot analysis. Therefore, celecoxib exerts its anti‐tumor activities through COX‐2‐independent mechanisms, which may be PI3K/Akt‐dependent, and survivin and bcl‐2‐related. PI3K may be at the center of the celecoxib effects, which play an essential role in the regulation of survivin and Bcl‐2.