[HTML][HTML] Celecoxib enhances anticancer effect of cisplatin and induces anoikis in osteosarcoma via PI3K/Akt pathway

B Liu, S Yan, L Qu, J Zhu - Cancer cell international, 2017 - Springer
B Liu, S Yan, L Qu, J Zhu
Cancer cell international, 2017Springer
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 …
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.
Conclusion
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.
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