Overexpression of cyclooxygenase-2 (COX-2) in human primitive neuroectodermal tumors: effect of celecoxib and

Ratnakar Patti1, Kiranmai Gumired, Pallu Reddanna

  • 1Division of Neuro-Oncology, Joseph Stokes Research Institute #515G, 3516 Civic Center Blvd, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Cancer Letters
|March 26, 2002
PubMed

Insights

Cyclooxygenase-2 (COX-2) inhibitors like celecoxib show potential in treating childhood primitive neuroectodermal tumors (PNETs). Celecoxib effectively suppressed tumor cell growth and modulated key proteins, offering a promising therapeutic avenue.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Primitive neuroectodermal tumors (PNETs) are aggressive childhood brain tumors.
  • Cyclooxygenase-2 (COX-2) is implicated in various cancers and may play a role in PNET development.

Purpose of the Study:

  • To investigate the role of COX-2 in PNETs.
  • To evaluate the efficacy of selective COX-2 inhibitors (celecoxib and rofecoxib) in inhibiting PNET cell growth.

Main Methods:

  • Analysis of COX-2 expression in human PNET samples and cell lines.
  • Treatment of PNET cell lines (DAOY and PFSK) with celecoxib and rofecoxib.
  • Assessment of cell growth inhibition, Bcl-2 expression, Akt, and caspase-3 activation.

Main Results:

  • COX-2 expression was significantly elevated in PNET samples compared to normal brain tissue.
  • Both celecoxib and rofecoxib inhibited PNET cell growth, with celecoxib demonstrating higher potency.
  • Celecoxib suppressed Akt expression and activated caspase-3, while rofecoxib did not exhibit these effects.
  • Growth inhibition was independent of Bcl-2 expression.

Conclusions:

  • COX-2 is highly expressed in PNETs and represents a potential therapeutic target.
  • Selective COX-2 inhibition, particularly with celecoxib, can suppress PNET cell proliferation.
  • Celecoxib's mechanism involves modulation of Akt and caspase-3 pathways, suggesting distinct therapeutic actions compared to rofecoxib.

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