Background/Objectives: Ketone esters (KEs) exhibit promise as anti-cancer agents but their impact on spontaneous metastases remains poorly understood. Although consumption of a ketogenic diet (KD) that is low in carbohydrates and high in fats can lead to KE production in vivo, the restrictive composition of KDs may diminish adherence in cancer patients. Methods: We investigated the effects of an exogenous ketone ester-supplemented (eKET), carbohydrate-replete diet on tumor growth, metastasis, and underlying mechanisms in orthotopic models of metastatic breast (4T1-Luc) and renal (Renca-Luc) carcinomas. Mice were randomized to diet after tumor challenge. Results: Administration of KEs did not alter tumor cell growth in vitro. However, in mice, our eKET diet increased circulating β-hydroxybutyrate and inhibited primary tumor growth and lung metastasis in both models. Body composition analysis illustrated the overall safety of eKET diet use, although it was associated with a loss of fat mass in mice with renal tumors. Immunogenetic profiling revealed divergent intratumoral eKET-related changes by tumor type. In mammary tumors, Wnt and TGFβ pathways were downregulated, whereas in renal tumors, genes related to hypoxia and DNA damage repair were downregulated. Conclusions: Thus, our eKET diet exerts potent antitumor and antimetastatic effects in both breast and renal cancer models, albeit with different modes of action and physiologic effects. Its potential as an adjuvant dietary approach for patients with diverse cancer types should be explored further.
背景/目的：酮酯类化合物作为抗癌药物展现出潜力，但其对自发性转移灶的影响尚不明确。虽然低碳水化合物、高脂肪的生酮饮食可在体内诱导酮酯生成，但其严格的饮食构成可能降低癌症患者的依从性。方法：本研究通过转移性乳腺癌（4T1-Luc）和肾癌（Renca-Luc）原位模型，探究外源性酮酯补充的碳水化合物充足饮食对肿瘤生长、转移及其潜在机制的影响。小鼠在肿瘤接种后随机分配饮食方案。结果：酮酯给药在体外未改变肿瘤细胞生长。然而在动物实验中，我们的酮酯补充饮食方案提升了循环β-羟基丁酸水平，并在两种模型中均抑制了原发性肿瘤生长和肺转移。身体成分分析显示该饮食方案总体安全，但在肾癌模型小鼠中观察到脂肪量减少。免疫遗传学分析揭示了不同肿瘤类型中瘤内酮酯相关变化的差异性：在乳腺肿瘤中Wnt和TGFβ通路下调，而在肾肿瘤中缺氧及DNA损伤修复相关基因表达降低。结论：本研究表明，酮酯补充饮食在乳腺癌和肾癌模型中均能发挥显著的抗肿瘤和抗转移作用，但其作用模式和生理效应存在差异。该方案作为针对不同癌症类型的辅助性膳食策略具有潜在价值，值得进一步探索。
An Exogenous Ketone Ester Slows Tumor Progression in Murine Breast and Renal Cancer Models
肿瘤(癌症)患者之家