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

Bing Liu1, Liyan Qu, Zhengming Yang

  • 1Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, PR China.

Medical Hypotheses
|May 2, 2012
PubMed

Insights

Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, triggers apoptosis in osteosarcoma cells by down-regulating PI3K/Akt. This COX-2 inhibition may reduce metastasis and benefit patients receiving standard therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cyclooxygenase-2 (COX-2) is implicated in inflammation and cancer development, with its overexpression common in osteosarcoma.
  • The PI3K/Akt pathway is crucial for cell adhesion and survival, and its dysregulation is linked to cancer progression.

Purpose of the Study:

  • To investigate whether COX-2 inhibitors induce anoikis (apoptosis due to detachment) in osteosarcoma cells.
  • To explore the role of the PI3K/Akt pathway in mediating the effects of COX-2 inhibition on cell adhesion and apoptosis.

Main Methods:

  • Treatment of human osteosarcoma MG-63 cells with Celecoxib, a COX-2 inhibitor.
  • Assessment of apoptosis markers, including DNA fragmentation, apoptotic bodies, caspase activation, and PARP cleavage.
  • Investigation of the PI3K/Akt pathway and expression of β-catenin, TrkB, and E-cadherin.
  • Use of wortmannin, a PI3K inhibitor, to mimic COX-2 inhibitor effects.

Main Results:

  • Celecoxib induced apoptosis in MG-63 cells, evidenced by DNA fragmentation, apoptotic bodies, activated caspases (8, 9), and cleaved PARP.
  • Celecoxib treatment led to the down-regulation of PI3K/Akt signaling.
  • The expression of β-catenin, TrkB, and E-cadherin was reduced, suggesting impaired cell-ECM and cell-cell adhesion.
  • Wortmannin mimicked the apoptotic effects of Celecoxib, supporting the role of PI3K/Akt inhibition.

Conclusions:

  • COX-2 inhibitors, like Celecoxib, induce apoptosis and anoikis in osteosarcoma cells, potentially through PI3K/Akt pathway down-regulation.
  • Inhibition of COX-2 may disrupt cell adhesion molecules (β-catenin, TrkB, E-cadherin), contributing to anoikis.
  • These findings suggest that COX-2 inhibitors could be a valuable addition to standard therapy for osteosarcoma, potentially reducing metastasis.

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