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基于GPX4的分子结构和特征对其在肿瘤靶向治疗中的功能进行研究。

Research on the function of GPX4 in tumor-targeted treatment based on its molecular structure and features.

作者信息

Geng He, Ma Lin, Wu Lixin, Yao Cuicui, Wang Can, Gan Xinyan, Li Yiyi, Chen Fang

机构信息

Department of Anaesthesiology, Shenzhen Children's Hospital, Shenzhen, China.

出版信息

Front Oncol. 2025 Sep 3;15:1594234. doi: 10.3389/fonc.2025.1594234. eCollection 2025.

Abstract

GPX4 is the only antioxidant enzyme in mammals that can convert cholesterol and phospholipid hydroperoxide into phosphatidylol and cholesterol. Its peculiar molecular structure allows it to perform a variety of biological functions, including oxidative stress, ferroptosis regulation, brain development stimulation, and immune responses. In recent years, several studies have demonstrated that increased GPX4 expression is linked to tumor cell proliferation, growth, migration, and differentiation. Overexpression of GPX4 has been linked to chemoresistance and a poor prognosis in cancers including nasopharyngeal carcinoma, breast cancer, and lung cancer. GPX4 inhibitors have been demonstrated to be effective in the treatment of numerous drug-resistant malignancies. Some tumors, such as glioblastoma, do not react well to single-agent GPX4 inhibitors. Therefore, future research should focus on identifying cancers that are more responsive to GPX4 inhibitors and enhancing the efficacy of these inhibitors. This research investigates the regulatory mechanisms and properties of GPX4 in various tumor cell types, as well as its molecular structure and biological roles, hoping to propose more effective tumor-targeted therapy alternatives.

摘要

谷胱甘肽过氧化物酶4(GPX4)是哺乳动物中唯一能将胆固醇和磷脂氢过氧化物转化为磷脂酰醇和胆固醇的抗氧化酶。其独特的分子结构使其能够执行多种生物学功能,包括氧化应激、铁死亡调节、促进大脑发育以及免疫反应。近年来,多项研究表明,GPX4表达增加与肿瘤细胞的增殖、生长、迁移和分化有关。GPX4的过表达与包括鼻咽癌、乳腺癌和肺癌在内的多种癌症的化疗耐药性及不良预后相关。已证明GPX4抑制剂在治疗多种耐药性恶性肿瘤方面有效。一些肿瘤,如胶质母细胞瘤,对单药GPX4抑制剂反应不佳。因此,未来的研究应集中于确定对GPX4抑制剂更敏感的癌症,并提高这些抑制剂的疗效。本研究调查了GPX4在各种肿瘤细胞类型中的调控机制和特性,以及其分子结构和生物学作用,希望能提出更有效的肿瘤靶向治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0636/12440787/459c1bf558a5/fonc-15-1594234-g001.jpg

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