Celecoxib inhibits Ewing sarcoma cell migration via actin modulation.

Area of Science:

• Oncology
• Cell Biology
• Pharmacology

Background:

• Ewing sarcoma (ES) is an aggressive childhood cancer with a high rate of metastasis and poor prognosis.
• Previous studies showed celecoxib reduces ES cell invasion and metastasis independently of cyclooxygenase-2.
• Celecoxib is known to affect β-catenin and the actin cytoskeleton, both implicated in tumor metastasis.

Purpose of the Study:

• To investigate whether celecoxib's antimetastatic effects in Ewing sarcoma are mediated by modulating β-catenin or the actin cytoskeleton.
• To elucidate the molecular mechanisms underlying celecoxib's action on ES cell invasion and migration.

Main Methods:

• Ewing sarcoma cells were treated with celecoxib.
• Western blot and qPCR were used to analyze β-catenin and actin levels.
• Small interfering RNA was used to deplete β-catenin, followed by invasion assays.
• Immunofluorescence staining and wound healing assays assessed cellular morphology, F-actin, and migration.

Main Results:

• Celecoxib significantly reduced total actin levels but did not affect β-catenin levels (mRNA or protein).
• Depletion of β-catenin did not impact invasion, and celecoxib's inhibitory effect persisted.
• Immunofluorescence showed reduced F-actin and altered cell morphology, but no change in β-catenin.
• Celecoxib significantly inhibited cell migration in wound healing assays.

Conclusions:

• Celecoxib's antimetastatic effect in Ewing sarcoma is not mediated by β-catenin.
• Celecoxib significantly modulates the actin cytoskeleton, leading to reduced invasion and migration.
• Targeting the actin cytoskeleton represents a potential therapeutic strategy for metastatic Ewing sarcoma.