Targeting angiogenic processes by combination rofecoxib and ionizing radiation

A P Dicker1, T L Williams, D S Grant

  • 1Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5097, USA.

Insights

Rofecoxib inhibits endothelial cell functions crucial for tumor growth. Combining rofecoxib with radiation therapy significantly enhances this inhibition, offering a potential strategy against angiogenesis-dependent cancers.

Area of Science:

  • Molecular Biology
  • Oncology
  • Pharmacology

Background:

  • Tumor growth and angiogenesis are closely linked processes.
  • Cyclooxygenase-2 (COX-2) plays a significant role in inflammation and cancer development.
  • COX-2 inhibitors like rofecoxib show efficacy in pain and inflammation management with reduced gastrointestinal risks.

Purpose of the Study:

  • To investigate the effects of rofecoxib, alone and in combination with radiation, on cytokine-induced angiogenesis in vitro.
  • To evaluate the potential of combining rofecoxib and radiation as an anti-angiogenic cancer therapy.

Main Methods:

  • In vitro assessment of cytokine-induced angiogenesis.
  • Evaluation of rofecoxib at various concentrations on endothelial cell proliferation, migration, and tube formation.
  • Assessment of the combined effect of rofecoxib and radiation on endothelial cell function.

Main Results:

  • Rofecoxib demonstrated dose-dependent inhibition of endothelial cell proliferation, migration, and tube formation at clinically relevant concentrations.
  • The combination of rofecoxib and radiation resulted in a twofold increase in the inhibition of endothelial cell function compared to rofecoxib alone.
  • These findings suggest a synergistic anti-angiogenic effect when rofecoxib and radiation are used together.

Conclusions:

  • Rofecoxib effectively inhibits key endothelial cell functions involved in angiogenesis.
  • The combination of rofecoxib and radiation presents a promising complementary strategy for targeting angiogenesis in malignancies.
  • This approach warrants further investigation for clinical applications in cancer treatment.

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