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[测量肿瘤细胞和肿瘤宿主生物体中14C-葡萄糖和14C-乙酸盐的氧化]

[Measuring 14C-glucose and 14C-acetate oxidation in tumour cells and tumorous host organism].

作者信息

Hujber Zoltán, Jeney András, Oláh Júlia, Szoboszlai Norbert, Baranyai Lajos, Környei József, Petõvári Gábor, Sebestyén Anna

机构信息

I. Sz. Patológiai és Kísérleti Rákkutató Intézet, Semmelweis Egyetem, Budapest, Hungary.

Kémiai Intézet, Eötvös Loránd Tudományegyetem, Analitikai Kémiai Tanszék, Budapest, Hungary.

出版信息

Magy Onkol. 2015 Dec;59(4):292-301. Epub 2015 Jul 30.

Abstract

Tumour cell metabolism can be influenced by alterations of the extracellular microenvironment and the tumour-promoting genetically changed mechanisms. There is increasing interest to introduce appropriate bioenergetic assays to describe the therapeutic effect and metabolic subtypes of tumours in clinical oncology. The analysis of 14C-glucose and 14C-acetate oxidation could be a suitable method to examine the metabolic/bioenergetic profiles of tumour cells and tumorous host organisms. The metabolic activity of tumour cells (in vitro cell lines, primary human lymphocytes and leukaemia cells) and the tumourous host organism were examined in vitro and in vivo by detecting the released CO2 levels derived from the radioactive carbon atom labelled energy substrates. We have found that the most cancer cells of solid tumours oxidised glucose more intensively than acetate. It was interesting that AML, CML and CLL cells isolated from blood preferred acetate as an energy substrate in vitro. Furthermore, based on our observations, tumours affected the glucose or acetate oxidation of the organism when applying bioenergetic substrates per os or iv. We provided the first data about the alterations in metabolic profiles of the tumour bearing organism in xenograft models. In summary, according to our results, comparison of the energy substrate oxidation can be an indicative method related to the metabolic profile analysis of tumour cells in vitro and tumorous host organism in vivo.

摘要

肿瘤细胞代谢会受到细胞外微环境改变和肿瘤促进基因改变机制的影响。在临床肿瘤学中,引入合适的生物能量测定法来描述肿瘤的治疗效果和代谢亚型的兴趣与日俱增。分析¹⁴C-葡萄糖和¹⁴C-乙酸盐氧化可能是一种检测肿瘤细胞和肿瘤宿主生物体代谢/生物能量特征的合适方法。通过检测源自放射性碳原子标记能量底物释放的二氧化碳水平,在体外和体内检测了肿瘤细胞(体外细胞系、原代人淋巴细胞和白血病细胞)以及肿瘤宿主生物体的代谢活性。我们发现,大多数实体瘤癌细胞氧化葡萄糖的程度比乙酸盐更强烈。有趣的是,从血液中分离出的急性髓细胞白血病(AML)、慢性髓细胞白血病(CML)和慢性淋巴细胞白血病(CLL)细胞在体外更喜欢将乙酸盐作为能量底物。此外,基于我们的观察,当经口或静脉内应用生物能量底物时,肿瘤会影响生物体对葡萄糖或乙酸盐的氧化。我们提供了异种移植模型中荷瘤生物体代谢特征改变的首批数据。总之,根据我们的结果,能量底物氧化的比较可以作为一种与体外肿瘤细胞和体内肿瘤宿主生物体代谢特征分析相关的指示性方法。

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