生酮饮食不会促进实验小鼠体内三阴性和腔隙性乳腺肿瘤的生长和转移

IF 4.2 3区 医学 Q2 ONCOLOGY Clinical & Experimental Metastasis Pub Date : 2023-12-09 DOI:10.1007/s10585-023-10249-z
Meret Grube, Arno Dimmler, Anja Schmaus, Rafael Saup, Tabea Wagner, Boyan K. Garvalov, Jonathan P. Sleeman, Wilko Thiele
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引用次数: 0

摘要

生酮饮食(KDs)可以改善乳腺癌患者的健康和生活质量。然而,有关生酮饮食对乳腺肿瘤影响的数据尚无定论,生酮饮食对转移的总体影响仍有待研究。因此,我们评估了KD对三阴性小鼠4T1乳腺肿瘤生长和转移的影响,以及对自体MMTV-PyMT小鼠模型中腔隙性乳腺肿瘤进展的影响。我们发现,生酮比率并不影响4T1和MMTV-PyMT乳腺肿瘤的转移,但会损害4T1肿瘤细胞在体内的增殖,并暂时降低4T1原发性肿瘤的生长。值得注意的是,小鼠诱导强效酮病所需的生酮比率(膳食脂肪与膳食碳水化合物和蛋白质的质量比)是人类的两倍。令人惊讶的是,只有雌性小鼠而非雄性小鼠对酮病有反应,血液中的β-羟丁酸水平持续上升。总之,我们的数据表明酮病不会促进原发性肿瘤的生长和转移,这表明酮病可以安全地应用于腔隙性乳腺癌,甚至可能对三阴性乳腺癌患者有利。此外,我们的数据还表明,在小鼠体内进行酮病实验时,必须验证诱导酮病所需的生酮比例,同时还应考虑小鼠的性别。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Ketogenic diet does not promote triple-negative and luminal mammary tumor growth and metastasis in experimental mice

Ketogenic diets (KDs) can improve the well-being and quality of life of breast cancer patients. However, data on the effects of KDs on mammary tumors are inconclusive, and the influence of KDs on metastasis in general remains to be investigated. We therefore assessed the impact of a KD on growth and metastasis of triple negative murine 4T1 mammary tumors, and on the progression of luminal breast tumors in an autochthonous MMTV-PyMT mouse model. We found that KD did not influence the metastasis of 4T1 and MMTV-PyMT mammary tumors, but impaired 4T1 tumor cell proliferation in vivo, and also temporarily reduced 4T1 primary tumor growth. Notably, the ketogenic ratio (the mass of dietary fat in relation to the mass of dietary carbohydrates and protein) that is needed to induce robust ketosis was twice as high in mice as compared to humans. Surprisingly, only female but not male mice responded to KD with a sustained increase in blood β-hydroxybutyrate levels. Together, our data show that ketosis does not foster primary tumor growth and metastasis, suggesting that KDs can be safely applied in the context of luminal breast cancer, and may even be advantageous for patients with triple negative tumors. Furthermore, our data indicate that when performing experiments with KDs in mice, the ketogenic ratio needed to induce ketosis must be verified, and the sex of the mice should also be taken into account.

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来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
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