肿瘤细胞抑制是抗癌研究的一个关键焦点，人们对 p53 的作用进行了广泛的研究。大量研究强调了它与活性氧 (ROS) 的密切关系。然而，抗氧化剂谷胱甘肽 (GSH) 在这方面的确切影响仍未得到充分阐明。在此，我们将阐明 GSH 治疗后 p53 介导的抗癌机制。在本研究中，我们在 SW480 结直肠细胞中采用 p53 基因敲除方法，并使用液相色谱-质谱联用技术对 20 种氨基酸和蛋白质组学进行了全面分析。质谱 (LC-MS/MS)。这些分析揭示了 GSH 处理引发的氨基酸和蛋白质的深刻变化，揭示了新现象并描绘了 GSH 和细胞蛋白质之间复杂的相互作用。 p53基因的缺失对肿瘤细胞的增殖产生深远的影响。此外，GSH 水平升高会显着影响肿瘤细胞增殖。重要的是，在缺乏 p53 基因的情况下，细胞对 GSH 表现出更高的敏感性，从而导致细胞生长受到抑制。涉及 GSH 和 p53 基因缺失的联合治疗方法可加速肿瘤细胞的死亡。值得注意的是，这种治疗会导致氨基酸代谢显着下降，特别是影响蛋氨酸（Met）和苯丙氨酸（Phe）氨基酸的下调。在 41 种表现出显着变化的蛋白质中，8 种表现出一致的变化，其中 5 种水平下降，3 种水平增加。这些蛋白质主要参与关键的细胞代谢过程和免疫功能。总之，GSH治疗和p53基因缺失的同时施用会引发肿瘤细胞的氨基酸和蛋白质代谢发生实质性改变，主要特征是下调。反过来，这会损害细胞代谢活动和免疫功能，最终导致肿瘤细胞死亡。这些新发现的见解具有广阔的前景，可以为开发直接有效的抗癌治疗铺平道路。2024 年胃肠肿瘤学杂志。版权所有。

Tumor cell inhibition is a pivotal focus in anti-cancer research, and extensive investigations have been conducted regarding the role of p53. Numerous studies have highlighted its close association with reactive oxygen species (ROS). However, the precise impact of the antioxidant glutathione (GSH) in this context remains inadequately elucidated. Here, we will elucidate the anti-cancer mechanisms mediated by p53 following treatment with GSH.In this study, we employed a p53 gene knockout approach in SW480 colorectal cells and conducted comprehensive analyses of 20 amino acids and proteomics using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).These analyses unveiled profound alterations in amino acids and proteins triggered by GSH treatment, shedding light on novel phenomena and delineating the intricate interplay between GSH and cellular proteins. The deletion of the p53 gene exerts a profound influence on tumor cell proliferation. Moreover, tumor cell proliferation is significantly affected by elevated GSH levels. Importantly, in the absence of the p53 gene, cells exhibit heightened sensitivity to GSH, leading to inhibited cell growth. The combined therapeutic approach involving GSH and p53 gene deletion expedites the demise of tumor cells. It is noteworthy that this treatment leads to a marked decline in amino acid metabolism, particularly affecting the down-regulation of methionine (Met) and phenylalanine (Phe) amino acids. Among the 41 proteins displaying significant changes, 8 exhibit consistent alterations, with 5 experiencing decreased levels and 3 demonstrating increased quantities. These proteins primarily participate in crucial cellular metabolic processes and immune functions.In conclusion, the concurrent administration of GSH treatment and p53 gene deletion triggers substantial modifications in the amino acid and protein metabolism of tumor cells, primarily characterized by down-regulation. This, in turn, compromises cell metabolic activity and immune function, ultimately culminating in the demise of tumor cells. These newfound insights hold promising implications and could pave the way for the development of straightforward and efficacious anti-cancer treatments.2024 Journal of Gastrointestinal Oncology. All rights reserved.