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首页> 外文期刊>Cell biology international. >Cancer cell sensitivity to arginine deprivation in vitro is not determined by endogenous levels of arginine metabolic enzymes.
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Cancer cell sensitivity to arginine deprivation in vitro is not determined by endogenous levels of arginine metabolic enzymes.

机译：癌细胞对精氨酸剥夺的体外敏感性不是由精氨酸代谢酶的内源性水平决定的。

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摘要

Single amino acid Arg (arginine) deprivation is currently considered as a therapeutic approach to treat certain types of tumours; the molecular mechanisms that underlie tumour cell sensitivity or resistance to Arg restriction are still little understood. Here, we address the question of whether endogenous levels of key Arg metabolic enzymes [catabolic: arginases, ARG1 (arginase type 1) and ARG2 (arginase type 2), and anabolic: OTC (ornithine transcarbamylase) and ASS (argininosuccinate synthetase)] affect cellular responses to arginine deprivation in vitro. Human epithelial cancer cells of different organs of origin exhibiting variable sensitivity to Arg deprivation provided the experimental models. Neither the basal expression status of the analysed enzymes, nor their changes upon arginine withdrawal correlated with cancer cell sensitivity to arginine deprivation. However, the ability to utilize exogenous Arg precursors (ornithine and citrulline) for growth in Arg-deficient medium strongly correlated with expression of the corresponding enzymes, OTC and ASS. We also observed that OTC expression was below the level of detection in all the types of tumour cells analysed, suggesting that in vitro, at least for them, Arg is an essential amino acid.
机译：目前，单氨基酸精氨酸剥夺被认为是治疗某些类型肿瘤的一种治疗方法。对肿瘤细胞敏感性或对Arg限制的抵抗力的分子机制仍知之甚少。在这里，我们解决关键Arg代谢酶[分解代谢：精氨酸酶，ARG1（精氨酸酶1型）和ARG2（精氨酸酶2型）和合成代谢：OTC（鸟氨酸转氨甲酰酶）和ASS（精氨酸琥珀酸合成酶）的内源水平是否受到影响的问题细胞对精氨酸剥夺的体外反应。实验结果表明，不同来源的人上皮癌细胞对Arg剥夺表现出不同的敏感性。所分析的酶的基础表达状态，或它们在精氨酸撤离后的变化均与癌细胞对精氨酸剥夺的敏感性无关。但是，利用外源性Arg前体（鸟氨酸和瓜氨酸）在缺乏Arg的培养基中生长的能力与相应酶OTC和ASS的表达密切相关。我们还观察到，在分析的所有类型的肿瘤细胞中，OTC表达均低于检测水平，这表明，至少在体外，对于他们而言，Arg是必需氨基酸。

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