Tirzepatide inhibits tumor growth in mice with diet-induced obesity

作者：Linxuan Huang, Jibin Zeng, Ye Wang, Michaël Pollak · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2023 · DOI：10.1101/2023.06.22.546093 · 被引用次数：5 · 研究领域：Metabolism, Diabetes, and Cancer、Diabetes Treatment and Management、Pancreatic and Hepatic Oncology Research

Abstract Tirzepatide, a drug used in management of type II diabetes, is an activator of both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptors. Tirzepatide treatment leads to weight loss in murine models of obesity, and clinical trials have shown the drug can lead to weight loss up to ∼ 20% in overweight patients. Obesity has been shown to increase risk and/or to worsen prognosis of certain common cancers, including colon cancer, but the effect of tirzepatide on neoplasia has not been examined in detail. We studied the effects of this drug on the murine MC38 colon cancer model, which has previously shown to exhibit accelerated growth in hosts with diet-induced obesity. Tirzepatide did not cause tumor regression, but reduced tumor growth rates by ∼ 50%. This was associated with substantial reductions in food intake, and in circulating levels of insulin and leptin. Tirzepatide had no effect on MC38 cancer cell proliferation in vitro , and the effect of tirzepatide on tumor growth in vivo could be phenocopied in placebo treated mice simply by restricting food intake to the amount consumed mice receiving the drug. This provides evidence that the drug acts indirectly to inhibit tumor growth. Our findings raise the possibility that use of tirzepatide or similar agents may benefit patients with obesity-related cancers.