title: Celecoxib enhances anticancer effect of cisplatin and induces anoikis in osteosarcoma via PI3K/Akt pathway.
abstract: 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, β-catenin were significantly downregulated in cells treated with the combination of celecoxib and cisplatin, and decreased β-catenin level was found in cells with wortmannin, a specific PI3K inhibitor.
  
  
  CONCLUSIONS
  Therefore, celecoxib enhances anticancer effect of cisplatin and induces anoikis in osteosarcoma, which may be PI3K/Akt-dependent, and MDR and β-catenin-related. PI3K may be at the center of the celecoxib effects, which play an essential role in the regulation of MDR and anoikis.
authors.affiliation: Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang People's Republic of China.
authors.forename: Shigui
authors.initials: S
authors.lastname: Yan
authors.affiliation: Clinical Laboratory Centre, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang People's Republic of China ; Clinical Laboratory Centre, Binjiang Hospital of Hangzhou, Hangzhou, Zhejiang People's Republic of China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
keywords: Anoikis; COX-2; MDR; Osteosarcoma; PI3K/Akt