本文選題：NADPH氧化酶NOX家族　切入點(diǎn)：腫瘤細(xì)胞　出處：《蘭州大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：NADPH氧化酶,又稱呼吸爆發(fā)氧化酶或巨噬細(xì)胞氧化酶,最早發(fā)現(xiàn)于中性粒細(xì)胞和巨噬細(xì)胞內(nèi),在病原物入侵時(shí),該酶被激活并產(chǎn)生大量活性氧(Reactive oxygen species, ROS)殺死病原微生物,所以在先天性免疫系統(tǒng)中發(fā)揮重要作用,但近年來(lái),大量研究表明該酶存在于幾乎所有的細(xì)胞中,與吞噬細(xì)胞中NADPH氧化酶生成的ROS主要起細(xì)胞防御功能不同的是,非吞噬細(xì)胞中NADPH氧化酶產(chǎn)生的ROS作為信號(hào)分子,參與機(jī)體內(nèi)信號(hào)轉(zhuǎn)導(dǎo),調(diào)節(jié)細(xì)胞分化、增殖、衰老和凋亡等活動(dòng)。NADPH氧化酶催化亞基gp91phox及其同源物統(tǒng)稱為NOX(包括NOX1-5)和DUOX(包括DUOX1和DUOX2),是該酶的核心亞基。研究發(fā)現(xiàn)在環(huán)境脅迫下,腫瘤細(xì)胞內(nèi)過量生成的ROS對(duì)蛋白質(zhì)、脂質(zhì)和核酸等細(xì)胞大分子造成不可逆性氧化損傷,最終能導(dǎo)致腫瘤細(xì)胞的死亡,但細(xì)胞內(nèi)ROS來(lái)源、NOX家族在ROS產(chǎn)生過程中的作用并不完全清楚。為了進(jìn)一步了解射線殺死腫瘤細(xì)胞的機(jī)理,尋找放射增敏的新靶點(diǎn),本實(shí)驗(yàn)研究了肺腺癌細(xì)胞系GLC-82、子宮頸癌細(xì)胞系HeLa、肝癌細(xì)胞系HepG2和前列腺癌細(xì)胞系PC-3等四種腫瘤細(xì)胞對(duì)X射線的敏感性,以及腫瘤細(xì)胞中NADPH氧化酶NOX家族蛋白表達(dá)及分布情況,并得出以下結(jié)論：①四種腫瘤細(xì)胞對(duì)相同劑量的X射線具有不同的敏感性；②NOX家族五個(gè)亞型在四種腫瘤細(xì)胞中均有表達(dá),但表達(dá)量不同；③NADPH氧化酶介導(dǎo)產(chǎn)生的ROS在射線誘導(dǎo)腫瘤細(xì)胞死亡過程中發(fā)揮重要作用；④細(xì)胞中不同NOX蛋白受到不同劑量X射線刺激時(shí)表達(dá)量不同；⑤不同細(xì)胞中相同NOX亞基蛋白受到相同劑量射線刺激時(shí)表達(dá)量不同；⑥腫瘤細(xì)胞對(duì)射線的敏感性可能由細(xì)胞內(nèi)NOX對(duì)射線的敏感性決定。 該研究發(fā)現(xiàn)NADPH氧化酶在射線殺死腫瘤細(xì)胞過程中的作用不可或缺,五種NOX家族蛋白在四種腫瘤細(xì)胞中表達(dá)量各不相同,在受到X射線輻照后,四種細(xì)胞中NOX家族表現(xiàn)出不同程度的激活,這些研究為放療增敏研究,以及對(duì)不同來(lái)源腫瘤細(xì)胞實(shí)施不同NOX家族蛋白定向調(diào)控以達(dá)到最佳的放療增敏效果提供了新的理論依據(jù)。
[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.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R730.55

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