本文選題：神經(jīng)母細(xì)胞瘤 + 雄激素受體�。� 參考：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:神經(jīng)母細(xì)胞瘤(neuroblastoma)是兒童最常見的發(fā)生在顱外的實體腫瘤。其主要起源于腎上腺,也可起源于腎上腺以外的交感神經(jīng)的其他部分,包括腹膜后或胸部。迄今導(dǎo)致神經(jīng)母細(xì)胞瘤發(fā)病的原因還不十分清楚,但是有些遺傳易感性因素被發(fā)現(xiàn)與神經(jīng)母細(xì)胞瘤的發(fā)病有關(guān)。目前關(guān)于神經(jīng)母細(xì)胞瘤的許多研究都在試圖尋找有效的治療這種惡性腫瘤的方法。雖然之前的一些報道已經(jīng)表明雄激素受體(AR)在神經(jīng)母細(xì)胞瘤細(xì)胞中有表達(dá),但是雄激素受體在神經(jīng)母細(xì)胞瘤中的生物學(xué)作用并不完全清楚。本研究將就雄激素受體信號通路對神經(jīng)母細(xì)胞瘤的調(diào)節(jié)作用進(jìn)行探討。并初步對中藥制劑復(fù)方木雞顆粒對神經(jīng)母細(xì)胞瘤的作用進(jìn)行觀察。方法:1.Western blot蛋白印跡法檢測雄激素受體(androgen receptor AR)在神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y,Neuro-2a)及其他細(xì)胞系以及轉(zhuǎn)染si RNA AR后的蛋白表達(dá)水平。2.MTT法檢測雄激素(R1881)、雄激素受體拮抗劑(MDV3100,ARN509)對神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y,Neuro-2a)增殖能力的影響;同時檢測中藥復(fù)方木雞顆粒對兩種不同細(xì)胞系293T(人腎上皮細(xì)胞系)和神經(jīng)母細(xì)胞瘤細(xì)胞系SH-SY5Y的IC50值的差異性。3.劃痕法檢測雄激素(R1881)、雄激素受體拮抗劑(MDV3100,ARN509)對神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y,Neuro-2a)遷移能力的影響。4.Transwell法檢測不同處理對神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y)侵襲能力的影響;5.3D成球?qū)嶒灪蛙洯傊湫纬蓪嶒灆z測不同處理對神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y,Neuro-2a)細(xì)胞球體形成能力的影響;6.裸鼠體內(nèi)種植神經(jīng)母細(xì)胞瘤細(xì)胞系Neuro-2a(N2a),檢測雄激素在體內(nèi)對神經(jīng)母細(xì)胞瘤的影響。結(jié)果:1.在神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y,N2a)檢測出雄激素受體(AR)有高表達(dá);2.雄激素促進(jìn)而雄激素受體拮抗劑抑制體外神經(jīng)母細(xì)胞瘤(SH-SY5Y,N2a)的增殖;3.雄激素促進(jìn)而雄激素受體拮抗劑抑制神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y,N2a)的遷移能力;4.雄激素促進(jìn)而雄激素受體拮抗劑抑制神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y)的侵襲能力;5.雄激素促進(jìn)神經(jīng)母細(xì)胞瘤細(xì)胞系(SH-SY5Y,N2a)細(xì)胞球體形成而雄激素受體拮抗劑抑制細(xì)胞球體形成的能力;6.雄激素促進(jìn)神經(jīng)母細(xì)胞瘤在裸鼠體內(nèi)(N2a)的生長。7.復(fù)方木雞顆粒處理后的293T和SH-SY5Y的IC50值有顯著學(xué)差異。結(jié)論:研究結(jié)果表明,雄激素受體信號通路可能參與了神經(jīng)母細(xì)胞瘤的進(jìn)展,并且這一發(fā)現(xiàn)可能為神經(jīng)母細(xì)胞瘤患者的診斷和治療提供新的靶點。復(fù)方木雞顆粒在體外能抑制神經(jīng)母細(xì)胞瘤(SH-SY5Y)生長,但其具體的作用機(jī)制還需要進(jìn)一步的研究。
[Abstract]:Background: neuroblastoma is the most common extracranial solid tumor in children. It originates mainly from the adrenal gland, but also from other parts of the sympathetic nerve other than the adrenal gland, including retroperitoneal or thoracic. So far, the causes of neuroblastoma are not well understood, but some genetic susceptibility factors have been found to be related to the pathogenesis of neuroblastoma. Many studies on neuroblastoma are trying to find effective treatment for this malignant tumor. Although previous reports have shown that androgen receptor ARs are expressed in neuroblastoma cells, the biological role of androgen receptors in neuroblastoma is not entirely clear. This study will explore the regulatory effects of androgen receptor signaling pathway on neuroblastoma. The effect of compound Muji granules on neuroblastoma was observed. Methods: 1. Western blot Western blot assay was used to detect the protein expression of androgen receptor in neuroblastoma cell line (SH-SY5YN Neuro-2a) and other cell lines. 2. Blot assay was used to detect the expression level of androgen receptor antagonist (R1881) and androgen receptor antagonist (TMDV3100ARN509) in neuroblastoma cell line (SH-SY5YN Neuro-2a) and after transfection of si RNA AR. The proliferation ability of SH-SY5YT Neuro-2a cell line was affected by transblastoma cell line (SH-SY5YN Neuro-2a). At the same time, the difference of IC50 value between two different cell lines 293T (human renal epithelial cell line) and neuroblastoma cell line (SH-SY5Y) was detected. Effect of scratching assay on migration ability of neuroblastoma cell line SH-SY5YN Neuro-2a in vitro. 4. Transwell method to detect the effect of different treatments on the invasiveness of neuroblastoma cell line SH-SY5Y5Y The effect of different treatments on the globular formation ability of neuroblastoma cell line SH-SY5YN Neuro-2a was detected by lipid colony forming assay. Neuroblastoma cell line Neuro-2a N2a was implanted in nude mice to detect the effect of androgen on neuroblastoma in vivo. The result is 1: 1. In neuroblastoma cell line SH-SY5YN _ 2a, androgen receptor (ARA) was found to be highly expressed in SH-SY5YN _ 2a cell line. Androgen stimulates and androgen receptor antagonist inhibits the proliferation of neuroblastoma SH-SY5YPN2a in vitro. Androgen promotes androgen receptor antagonist inhibits the migration of neuroblastoma cell line SH-SY5YON2a. Androgen promotes androgen receptor antagonist inhibits invasion of neuroblastoma cell line SH-SY5Y. Androgen promotes the formation of spheroid in neuroblastoma cell line SH-SY5YN _ 2a, and androgen receptor antagonist inhibits the formation of cell sphere. Androgen promotes the growth of neuroblastoma in nude mice. The IC50 values of 293T and SH-SY5Y treated with compound Muji granules were significantly different. Conclusion: the results suggest that the androgen receptor signaling pathway may be involved in the progression of neuroblastoma, and this discovery may provide a new target for the diagnosis and treatment of neuroblastoma. Compound Muji granules can inhibit the growth of neuroblastoma SH-SY5Y in vitro, but its specific mechanism needs further study.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R739.4

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