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Celecoxib as a Valuable Adjuvant in Cutaneous Melanoma Treated with Trametinib

Diana Valentina Tudor1, Ioana Bâldea1, Diana Elena Olteanu1

  • 1Department of Physiology, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

International Journal of Molecular Sciences
|April 30, 2021
PubMed
Abstract

Insights

Low-dose celecoxib enhances melanoma treatment with trametinib by inhibiting key pathways and promoting cell death. This combination therapy offers a promising approach for overcoming drug resistance in metastatic melanoma.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Melanoma treatment resistance often involves MAPK pathway reactivation, PI3K/mTOR pathway activation, or stromal cell interactions.
  • Combinational therapeutic strategies are crucial for future melanoma treatment advancements.

Purpose of the Study:

  • To investigate if low-dose celecoxib (in the nM range) can preserve chemopreventive effects when combined with trametinib in melanoma cells.
  • To evaluate the impact of this combination on cell death, melanogenesis, angiogenesis, inflammation, and resistance pathways.

Main Methods:

  • Experiments utilized SK-MEL-28 human melanoma cells and BJ human fibroblasts in co-culture.
  • Co-cultures were treated with a combination of celecoxib and trametinib for 72 hours.
  • Analysis focused on cell death mechanisms, melanogenesis, angiogenesis, inflammation, and resistance pathways.

Main Results:

  • Low-dose celecoxib significantly potentiated melanoma cell response to trametinib.
  • The combination therapy reduced nuclear transcription factor-kappa B (NF-kB) and induced caspase-8/caspase-3 activation.
  • Microphthalmia transcription factor (MITF) and tyrosinase expression were inhibited, and the PI3K/AKT signaling pathway was significantly downregulated.

Conclusions:

  • Low celecoxib concentrations (nM range) demonstrated antineoplastic activity.
  • The combination of low-dose celecoxib and trametinib enhanced the therapeutic efficacy against metastatic melanoma.
Keywords:
COX-2celecoxibinflammationmelanomatrametinib

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