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NOX家族蛋白在射线杀死肿瘤细胞中的作用

发布时间:2018-03-05 18:21

  本文选题:NADPH氧化酶NOX家族 切入点:肿瘤细胞 出处:《兰州大学》2012年硕士论文 论文类型:学位论文


【摘要】:NADPH氧化酶,又称呼吸爆发氧化酶或巨噬细胞氧化酶,最早发现于中性粒细胞和巨噬细胞内,在病原物入侵时,该酶被激活并产生大量活性氧(Reactive oxygen species, ROS)杀死病原微生物,所以在先天性免疫系统中发挥重要作用,但近年来,大量研究表明该酶存在于几乎所有的细胞中,与吞噬细胞中NADPH氧化酶生成的ROS主要起细胞防御功能不同的是,非吞噬细胞中NADPH氧化酶产生的ROS作为信号分子,参与机体内信号转导,调节细胞分化、增殖、衰老和凋亡等活动。NADPH氧化酶催化亚基gp91phox及其同源物统称为NOX(包括NOX1-5)和DUOX(包括DUOX1和DUOX2),是该酶的核心亚基。研究发现在环境胁迫下,肿瘤细胞内过量生成的ROS对蛋白质、脂质和核酸等细胞大分子造成不可逆性氧化损伤,最终能导致肿瘤细胞的死亡,但细胞内ROS来源、NOX家族在ROS产生过程中的作用并不完全清楚。为了进一步了解射线杀死肿瘤细胞的机理,寻找放射增敏的新靶点,本实验研究了肺腺癌细胞系GLC-82、子宫颈癌细胞系HeLa、肝癌细胞系HepG2和前列腺癌细胞系PC-3等四种肿瘤细胞对X射线的敏感性,以及肿瘤细胞中NADPH氧化酶NOX家族蛋白表达及分布情况,并得出以下结论:①四种肿瘤细胞对相同剂量的X射线具有不同的敏感性;②NOX家族五个亚型在四种肿瘤细胞中均有表达,但表达量不同;③NADPH氧化酶介导产生的ROS在射线诱导肿瘤细胞死亡过程中发挥重要作用;④细胞中不同NOX蛋白受到不同剂量X射线刺激时表达量不同;⑤不同细胞中相同NOX亚基蛋白受到相同剂量射线刺激时表达量不同;⑥肿瘤细胞对射线的敏感性可能由细胞内NOX对射线的敏感性决定。 该研究发现NADPH氧化酶在射线杀死肿瘤细胞过程中的作用不可或缺,五种NOX家族蛋白在四种肿瘤细胞中表达量各不相同,在受到X射线辐照后,四种细胞中NOX家族表现出不同程度的激活,这些研究为放疗增敏研究,以及对不同来源肿瘤细胞实施不同NOX家族蛋白定向调控以达到最佳的放疗增敏效果提供了新的理论依据。
[Abstract]:NADPH oxidase, also called respiratory burst oxidase or macrophage oxidase, was first found in neutrophils and macrophages. When the pathogen invaded, the enzyme was activated and produced a large number of reactive oxygen speciesto kill pathogenic microorganisms. So it plays an important role in the innate immune system, but in recent years, a large number of studies have shown that the enzyme exists in almost all cells, which is different from the ROS produced by NADPH oxidase in phagocytes. ROS produced by NADPH oxidase in non-phagocytes is a signal molecule involved in signal transduction, regulating cell differentiation and proliferation. Activities such as senescence and apoptosis. NADPH-Oxidase catalytic subunit gp91phox and its congeners NOX (including NOX1-5) and DUOX2 (including DUOX1 and DUOX2) are the core subunits of this enzyme. Cellular macromolecules such as lipids and nucleic acids cause irreversible oxidative damage and eventually lead to tumor cell death. However, the role of the ROS family in the production of ROS is not completely clear. In order to further understand the mechanism of radiation killing tumor cells, we seek new targets for radiosensitization. In this study, we studied the X ray sensitivity of four kinds of tumor cells: lung adenocarcinoma cell line GLC-82, cervical cancer cell line HeLa, hepatocellular carcinoma cell line HepG2 and prostate cancer cell line PC-3, and the expression and distribution of NADPH oxidase NOX family proteins in tumor cells. It is concluded that the four tumor cells have different sensitivities to the same dose of X-rays and the five subtypes of the family are all expressed in the four kinds of tumor cells. However, the expression of ROS mediated by NADPH oxidase plays an important role in radiation-induced death of tumor cells. Different NOX proteins are expressed in different doses of X-rays. The expression levels are the same in different cells. The radiosensitivity of tumor cells with different amounts of NOX subunit protein stimulated by the same dose of radiation may be determined by the radiosensitivity of intracellular NOX to radiation. This study found that NADPH oxidase plays an indispensable role in the process of radiation killing tumor cells. The expression of five NOX family proteins in four kinds of tumor cells is different. The NOX family showed different activation in four kinds of cells. These studies provided a new theoretical basis for radiosensitization and the directional regulation of different NOX family proteins in different tumor cells in order to achieve the best radiosensitization effect.
【学位授予单位】:兰州大学
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R730.55

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