Glenny Elaine M, Ho Alyssa N, Kiesel Violet A, Chen Fangxin, Gates Claire E, Paules Evan M, Xu Ruihan, Holt C Alex, Coleman Michael F, Hursting Stephen D
Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
bioRxiv. 2024 Jan 23:2024.01.20.576484. doi: 10.1101/2024.01.20.576484.
We report for the first time an anticancer benefit of tirzepatide-a dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist-in a model of obesity and breast cancer in female mice. Long-term tirzepatide treatment induced weight loss, mitigated obesity-driven changes in circulating metabolic hormone levels, and suppressed orthotopic E0771 mammary tumor growth. Relative to tirzepatide, chronic calorie restriction, an established anticancer intervention in preclinical models, promoted even greater weight loss, systemic hormonal regulation, and tumor suppression. We conclude that tirzepatide represents a promising pharmacologic approach for mitigating the procancer effects of obesity. Moreover, strategies promoting greater weight loss than achieved with tirzepatide alone may augment the anticancer benefits of tirzepatide.
我们首次报告了替尔泊肽（一种双重胰高血糖素样肽-1和葡萄糖依赖性促胰岛素多肽受体激动剂）在雌性小鼠肥胖和乳腺癌模型中的抗癌益处。长期使用替尔泊肽治疗可导致体重减轻，减轻肥胖驱动的循环代谢激素水平变化，并抑制原位E0771乳腺肿瘤生长。相对于替尔泊肽，长期热量限制（一种在临床前模型中已确立的抗癌干预措施）可促进更大程度的体重减轻、全身激素调节和肿瘤抑制。我们得出结论，替尔泊肽是一种有前景的减轻肥胖促癌作用的药理学方法。此外，比单独使用替尔泊肽能促进更大程度体重减轻的策略可能会增强替尔泊肽的抗癌益处。
