常氧和低氧低糖条件下β-羟基丁酸和α-酮戊二酸对HCT-116结直肠癌细胞活力的差异影响:探讨SRC、HIF1α、ACAT1和SIRT2基因的作用。

IF 2.3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Genetics and Genomics Pub Date : 2025-01-20 DOI:10.1007/s00438-024-02211-9
Parisa Badameh, Farideh Akhlaghi Tabar, Nima Mohammadipoor, Roya Rezaei, Roza Ranjkesh, Mohammad Hasan Maleki, Omid Vakili, Sayed Mohammad Shafiee
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引用次数: 0

摘要

最近的治疗策略强调了β-羟基丁酸酯(BHB)和α-酮戊二酸酯(α-KG)作为有效抗癌药物的潜力,特别是对结肠癌。这些代谢物可以调节细胞代谢,诱导表观遗传变化,抑制肿瘤生长。然而,在缺氧条件下,某些癌细胞可能会利用BHB等酮体作为营养来源,从而可能降低治疗效果。了解这些机制对于优化癌症治疗至关重要。本研究考察了BHB和α-KG对常氧和低糖缺氧条件下HCT-116结直肠癌细胞活力的影响。用不同剂量的BHB和α-KG处理HCT-116细胞株,在常氧和低糖缺氧条件下,采用MTT法测定细胞活力。此外,采用定量逆转录聚合酶链式反应(RT-PCR)检测SRC、缺氧诱导因子1α (HIF-1α)、乙酰辅酶a乙酰转移酶1 (ACAT1)和sirtuin 2 (SIRT2)基因的mRNA表达水平。BHB在低糖缺氧条件下显著增加HCT-116结肠癌细胞的增殖,而α-KG在常氧条件下维持细胞活力,而在缺氧条件下没有作用。BHB治疗降低了SIRT2 mRNA水平,增加了ACAT1、SRC和HIF-1α的表达。相反,α-KG降低常氧状态下ACAT1、SRC和HIF-1α的表达,升高SIRT2水平,但在缺氧状态下不能逆转基因表达。我们的研究表明,在不同的氧气和葡萄糖条件下,BHB和α-KG与结肠癌细胞活力表现出复杂的相互作用。BHB在缺氧条件下促进细胞增殖,α-KG在常氧条件下具有保护作用。这项研究为支持代谢调节剂在癌症治疗中的作用提供了越来越多的证据,并强调了了解肿瘤微环境对优化治疗结果的重要性。然而,需要进一步研究代谢途径,以加强癌症治疗的治疗策略。
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Differential effects of β-hydroxybutyrate and α-ketoglutarate on HCT-116 colorectal cancer cell viability under normoxic and hypoxic low-glucose conditions: exploring the role of SRC, HIF1α, ACAT1, and SIRT2 genes.

Recent therapeutic strategies have highlighted the potential of β-hydroxybutyrate (BHB) and α-ketoglutarate (α-KG) as effective anticancer agents, particularly for colon cancer. These metabolites can modulate cellular metabolism and induce epigenetic changes, inhibiting tumor growth. Nonetheless, certain cancer cells may utilize ketone bodies, like BHB as nutrient sources under hypoxic conditions, potentially reducing treatment efficacy. Understanding these mechanisms is crucial for optimizing cancer therapies. This study evaluated the effects of BHB and α-KG on HCT-116 colorectal cancer cell viability under normoxic and low-glucose hypoxic conditions. HCT-116 cell lines were treated with different doses of BHB and α-KG in normoxic and low-glucose hypoxic conditions, and then cell viability was assessed by the MTT assay. Moreover, the mRNA expression levels of SRC, hypoxia-inducible factor 1α (HIF-1α), acetyl-CoA acetyltransferase 1 (ACAT1), and sirtuin 2 (SIRT2) genes were determined using quantitative reverse transcriptase-polymerase chain reaction (q RT-PCR). BHB significantly increased the proliferation of HCT-116 colon cancer cells under low-glucose hypoxic conditions, while α-KG maintained cell viability in normoxic conditions but not in hypoxia. BHB treatment reduced SIRT2 mRNA levels and increased ACAT1, SRC, and HIF-1α expression. Conversely, α-KG decreased ACAT1, SRC, and HIF-1α expression and increased SIRT2 levels in normoxia but could not reverse gene expression during hypoxia. Our study demonstrated that BHB and α-KG exhibited complex interactions with colon cancer cell viability under varying oxygen and glucose conditions. While BHB promoted cell proliferation in hypoxic environments, α-KG showed protective effects in normoxic conditions. This research contributed to the growing body of evidence supporting the role of metabolic modulators in cancer therapy and emphasized the importance of understanding tumor microenvironments to optimize treatment outcomes. However, the need for further research into the metabolic pathways is underscored to enhance therapeutic strategies for cancer treatment.

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来源期刊
Molecular Genetics and Genomics
Molecular Genetics and Genomics 生物-生化与分子生物学
CiteScore
5.10
自引率
3.20%
发文量
134
审稿时长
1 months
期刊介绍: Molecular Genetics and Genomics (MGG) publishes peer-reviewed articles covering all areas of genetics and genomics. Any approach to the study of genes and genomes is considered, be it experimental, theoretical or synthetic. MGG publishes research on all organisms that is of broad interest to those working in the fields of genetics, genomics, biology, medicine and biotechnology. The journal investigates a broad range of topics, including these from recent issues: mechanisms for extending longevity in a variety of organisms; screening of yeast metal homeostasis genes involved in mitochondrial functions; molecular mapping of cultivar-specific avirulence genes in the rice blast fungus and more.
期刊最新文献
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