Calvo-Anguiano Geovana, Lugo-Trampe Jose J, Camacho Alberto, Said-Fernández Salvador, Mercado-Hernández Roberto, Zomosa-Signoret Viviana, Rojas-Martínez Augusto, Ortiz-López Rocio
Biochemistry and Molecular Medicine Department, School of Medicine, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo León 64460, Mexico.
Center for Research and Development in Health Sciences, Genomic Unit, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo León 64460, Mexico.
Exp Ther Med. 2018 Jun;15(6):4777-4784. doi: 10.3892/etm.2018.6048. Epub 2018 Apr 10.
The microenvironment plays a fundamental role in carcinogenesis: Acidity and hypoxia are actively involved in this process. It is important to have models to study these mechanisms. The models that are most commonly referred to are the hypoxia chamber and the chemical induction [Cobalt (II) chloride]. It is not yet defined if these models are interchangeable if the metabolic effect is the same, and if the results may be compared in these models. In the present study, the response to the effect of stress (hypoxia and acidity) in both models was evaluated. The results indicated that in the chemical model, the effect of hypoxia appeared in an early form at 6 h; whereas in the gas chamber the effect was slow and gradual and at 72 h there was an overexpression of erythropoietin (), vascular endothelial growth factor (), carbonic anhydrase 9 () and hypoxia-inducible factor 1α (). In addition to the genes analyzed by reverse transcription-quantitative polymerase chain reaction, the global expression analysis between both models revealed the 9 most affected genes in common. The present study additionally identified 3 potential genes (lysyl oxidase, ankyrin repeat domain 37, B-cell lymphoma 2 interacting protein 3 like) previously identified in other studies, which may be considered as universal hypoxia genes along with , glucose transporter 1 (), , and . To the best of the author's knowledge, this is the first time that both hypoxia models have been compared, and it was demonstrated that the effect of hypoxia induction was time sensitive in each model. These observations must be considered prior to selecting one of these models to identify selective hypoxia genes and their effects in cancer.
酸性和缺氧积极参与这一过程。拥有研究这些机制的模型很重要。最常提及的模型是缺氧箱和化学诱导(氯化钴)。如果代谢效应相同,以及这些模型的结果是否可以比较,目前尚未明确这些模型是否可互换。在本研究中,评估了两种模型对应激(缺氧和酸性)效应的反应。结果表明,在化学模型中,缺氧效应在6小时时以早期形式出现;而在气箱模型中,效应缓慢且渐进,在72小时时促红细胞生成素、血管内皮生长因子、碳酸酐酶9和缺氧诱导因子1α出现过表达。除了通过逆转录定量聚合酶链反应分析的基因外,两种模型之间的整体表达分析揭示了9个最受影响的共同基因。本研究还鉴定了先前在其他研究中确定的3个潜在基因(赖氨酰氧化酶、锚蛋白重复结构域37、B细胞淋巴瘤2相互作用蛋白3样),它们可能与葡萄糖转运蛋白1、碳酸酐酶9、缺氧诱导因子1α一起被视为普遍的缺氧基因。据作者所知,这是首次对两种缺氧模型进行比较,并且证明了缺氧诱导效应在每个模型中对时间敏感。在选择这些模型之一以鉴定选择性缺氧基因及其在癌症中的作用之前,必须考虑这些观察结果。