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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.
Abstract:
In this study the role of cyclooxygenase-2 (COX-2) in primitive neuroectodermal tumor (PNET) the most malignant brain tumors of childhood was investigated. COX-2 expression in human brain tumor biopsy samples (seven/seven) was about 6-8-fold higher than normal brain tissue and several PNET cell lines also express COX-2. The effect of selective COX-2 inhibitors, celecoxib and rofecoxib on the growth of two PNET cell lines (DAOY and PFSK) was determined. Celecoxib was more potent than rofecoxib in suppressing cell growth. Growth inhibition by celecoxib and rofecoxib was independent of Bcl-2 expression. Celecoxib suppressed the expression of Akt and activated the caspase-3 in DAOY and PFSK, whereas rofecoxib did not have such an effect.
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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