研究动态
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乳腺癌细胞中β-羟基丁酸治疗的代谢改变和细胞反应。

Metabolic alterations and cellular responses to β-Hydroxybutyrate treatment in breast cancer cells.

发表日期:2024 May 29
作者: Hadas Fulman-Levy, Raichel Cohen-Harazi, Bar Levi, Lital Argaev-Frenkel, Ifat Abramovich, Eyal Gottlieb, Sarah Hofmann, Igor Koman, Elimelech Nesher
来源: Cellular & Molecular Immunology

摘要:

生酮饮食 (KD) 以高脂肪(超过每日卡路里的 70%)、低碳水化合物和充足的蛋白质摄入为基础,由于其对包括癌症在内的多种疾病的潜在治疗益处而变得流行。在 KD 和饥饿条件下,碳水化合物的缺乏会促进肝脏从脂肪中产生酮体 (KB),作为代谢能量的替代来源。 KD 和饥饿可能会影响癌细胞的新陈代谢以及肿瘤特征。本研究的目的是在体外评估 KD 条件对乳腺癌细胞各个方面的影响。使用两种癌症和一种非癌症乳腺癌细胞系,我们评估 β-羟基丁酸 (βHb) 治疗的效果细胞生长、存活、增殖、集落形成和迁移。我们还评估了 KB 对细胞代谢特征的影响。使用RNAseq分析,我们阐明了βHb对基因表达谱的影响。βHb处理后观察到显着的影响,包括对MCF7细胞的活力、增殖和集落形成的影响,以及对MDA-MB-集落形成的不同影响。 231 细胞,对非癌症 HB2 细胞没有这种影响。通过 LC-MS 测量,我们发现 βHb 治疗后葡萄糖摄入量或乳酸排出量没有变化,但检测到活性氧 (ROS) 水平增加。 RNAseq 分析表明参与脂质代谢、癌症和氧化磷酸化的基因发生显着变化。根据我们的结果,我们得出结论,癌细胞系对 βHb 治疗的差异反应作为改变脂质代谢和致癌性的替代能源或信号,支持乳腺癌患者治疗需要个性化方法。© 2024。作者。
The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells in vitro.Using two cancer and one non-cancer breast cell line, we evaluate the effect of β-hydroxybutyrate (βHb) treatment on cell growth, survival, proliferation, colony formation, and migration. We also assess the effect of KB on metabolic profile of the cells. Using RNAseq analysis, we elucidate the effect of βHb on the gene expression profile.Significant effects were observed following treatment by βHb which include effects on viability, proliferation, and colony formation of MCF7 cells, and different effects on colony formation of MDA-MB-231 cells, with no such effects on non-cancer HB2 cells. We found no changes in glucose intake or lactate output following βHb treatment as measured by LC-MS, but an increase in reactive oxygen species (ROS) level was detected. RNAseq analysis demonstrated significant changes in genes involved in lipid metabolism, cancer, and oxidative phosphorylation.Based on our results, we conclude that differential response of cancer cell lines to βHb treatment, as alternative energy source or signal to alter lipid metabolism and oncogenicity, supports the need for a personalized approach to breast cancer patient treatment.© 2024. The Author(s).