Atasoy Ozum, Anadol Elvan, Yar Saglam Atiye Seda, Akdemir Eyub Yasar, Coskun Yasemin Sengun, Atak Ece, Dincer Sefika, Usta Duygu Deniz, Emniyet Sert Aslı, Kaplanoglu Gulnur Take, Guney Yıldız
Department of Radiation Oncology, Giresun Research and Training Hospital, Giresun, Turkiye.
Department of Medical Biochemistry, İstanbul Medeniyet University, School of Medicine, Istanbul, Turkiye.
Curr Radiopharm. 2025;18(4):318-332. doi: 10.2174/0118744710381356250429045716.
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.
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.
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.
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.
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.
胰高血糖素样肽-1受体激动剂（GLP-1 RAs）是一类抗糖尿病药物，以其抗炎和抗氧化特性而闻名。本研究在临床前小鼠模型中探究了GLP-1 RAs与放射治疗（RT）对乳腺癌的协同作用。
将4T1乳腺癌细胞接种到雌性BALB/c小鼠体内，并分为五组：对照组、安慰剂组、单独使用GLP-1 RA组、单独使用RT组和联合治疗组。通过腹腔注射给予GLP-1 RA，并施加单次8 Gy的RT剂量。评估肿瘤体积、组织病理学变化、细胞因子表达和凋亡相关蛋白谱。在体外，评估GLP-1 RA和/或RT处理后4T1细胞的活力。
与单独使用RT或GLP-1 RA相比，联合治疗显著减小了肿瘤体积。组织学分析显示联合治疗方法改善了组织形态。免疫组织化学染色显示促炎标志物（IL-6、TNF-α）和血管生成因子（VEGF-A、FGF-2）的表达降低，而促凋亡蛋白（caspase-3、BAD、p53）升高。体外研究结果证实联合治疗可协同降低细胞活力。
结果表明，GLP-1 RAs增强了RT对乳腺癌的抗肿瘤作用，主要是通过调节细胞凋亡和肿瘤微环境实现的。
GLP-1 RAs可能是乳腺癌RT的有效辅助剂，特别是对于糖尿病患者。肿瘤增敏和保护正常组织的双重益处提供了一条有前景的治疗途径。
