Synergistic Potential of GLP-1 Receptor Agonists and Radiotherapy in Breast Cancer Treatment: A New Therapeutic Avenue (TROD-GROG 006)


Atasoy Ö., ANADOL E., YAR SAĞLAM A. S., Akdemir E. Y., Coşkun Y. Ş., Atak E., ...Daha Fazla

Current Radiopharmaceuticals, cilt.18, sa.4, ss.318-332, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 18 Sayı: 4
  • Basım Tarihi: 2025
  • Doi Numarası: 10.2174/0118744710381356250429045716
  • Dergi Adı: Current Radiopharmaceuticals
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.318-332
  • Anahtar Kelimeler: angiogenesis, apoptosis, breast cancer, cytokines, exenatide, GLP-1 receptor agonists, radiotherapy, tumor microenvironment
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

Introduction: GLP-1 receptor agonists (GLP-1 RAs) are anti-diabetic agents known for their anti-inflammatory and antioxidant properties. This study investigates the synergistic effects of GLP-1 RAs and radiotherapy (RT) on breast cancer in a preclinical mouse model. Materials and Methods: Female BALB/c mice were inoculated with 4T1 breast cancer cells and divided into five groups: control, placebo, GLP-1 RA alone, RT alone, and combination treatment. GLP-1 RA was administered intraperitoneally, and a single 8 Gy RT dose was applied. Tumor volumes, histopathological changes, cytokine expression, and apoptosis-related protein profiles were evaluated. In vitro, 4T1 cell viability was assessed following GLP-1 RA and/or RT exposure. Results: Combination therapy significantly reduced tumor volume compared to RT or GLP-1 RA alone. Histological analysis revealed improved tissue morphology with the combined approach. Immunohistochemical staining showed decreased expression of pro-inflammatory markers (IL-6, TNF-α) and angiogenic factors (VEGF-A, FGF-2), while pro-apoptotic proteins (caspase-3, BAD, p53) were elevated. In vitro findings confirmed a synergistic reduction in cell viability with combined treatment. Discussion: The results indicate that GLP-1 RAs potentiate the antitumor effect of RT in breast cancer, primarily through modulation of apoptosis and the tumor microenvironment. Conclusion: GLP-1 RAs may be effective adjuvants to RT in breast cancer, particularly for patients with diabetes. The dual benefit of tumor sensitization and protection of normal tissues offers a promising therapeutic avenue.