期刊
CANCER CELL INTERNATIONAL
卷 17, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12935-016-0378-2
关键词
COX-2; MDR; Anoikis; PI3K/Akt; Osteosarcoma
类别
资金
- Medical science and technology project of Zhejiang province of china [2016KYA096]
- Natural Science Funds of Zhejiang Province [Y17H160033]
Background: COX-2, an inducible enzyme, is associated with inflammatory diseases and carcinogenesis. Overexpression of COX-2 occurs in many human malignancies, including osteosarcoma. COX-2 positivity is form 67 to 92% in osteosarcoma, and COX-2 expresses 141-fold more in cancer stem cell spheres than daughter adherent cells. In our study, we have reported that celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt. It has been confirmed that celecoxib enhances apoptosis and cytotoxic effect of cisplatin, although the mechanism remains unclear. Methods: 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. Results: MDR1, MRP1, BCRP and Trkb, E-cadherin, beta-catenin were significantly downregulated in cells treated with the combination of celecoxib and cisplatin, and decreased beta-catenin level was found in cells with wortmannin, a specific PI3K inhibitor. Conclusion: Therefore, celecoxib enhances anticancer effect of cisplatin and induces anoikis in osteosarcoma, which may be PI3K/Akt-dependent, and MDR and beta-catenin-related. PI3K may be at the center of the celecoxib effects, which play an essential role in the regulation of MDR and anoikis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据