β2肾上腺素受体通过Hedgehog信号通路对前列腺癌影响的研究

发布时间：2018-06-06 12:46

本文选题：前列腺癌 + β2肾上腺素受体　；参考：《重庆医科大学》2017年硕士论文

【摘要】：实验目的:研究自主神经β2肾上腺素受体(β-2 Adrenergic receptor,ADRB2)在前列腺癌组织中的表达情况与临床病理特征转归特征的关系,并通过体外细胞实验初步探讨ADRB2在前列腺癌发展中的潜在作用机制。实验方法:1.采用免疫组织化学和组织微序列的方法检测正常前列腺组织和前列腺癌组织的ADRB2蛋白的表达情况,分析其表达差异性及其与临床病理转归特征的关系。2.ADRB2激动剂异丙肾上腺素和阻断剂普萘洛尔作用于前列腺癌PC-3细胞后,用MTT实验、Hoechst、流式细胞技术检测其对细胞增殖和凋亡的影响。3.免疫组织化学方法检测前列腺癌中Hedgehog信号通路相关信号因子Shh、Ptch、Gli1的表达情况,分析ADRB2与其相关性。异丙肾上腺素和普萘洛尔处理前列腺癌细胞PC-3细胞后,用实时荧光定量PCR法和Western-Blot法检测Shh、Ptch、Gli1的变化情况。实验结果:1.与正常的前列腺组织相比,前列腺癌组织中β2肾上腺素受体的表达明显增多。β2肾上腺素受体的表达强度与前列腺癌的病理分级、临床分期、有无转移有一定的相关性。2.β2肾上腺素受体激动剂异丙肾上腺素能促进前列腺癌PC-3细胞的增殖,阻断剂能抑制其增殖作用;普萘洛尔能够促进前列腺癌细胞PC-3的凋亡。3.在前列腺组织中,ADRB2的表达强度与Ptch的表达强度呈正相关。异丙肾上腺素处理前列腺癌细胞PC-3后,Hh信号通路的相关信号蛋白Shh、Ptch、Gli1的表达量升高,普萘洛尔处理后PC-3细胞的Shh、Ptch、Gli1表达量下降。实验结论:交感神经可能通过对β2肾上腺素受体来参与前列腺癌发生发展的过程,并且这种影响作用可能与Hh信号通路的激活或加强有关。
[Abstract]:Objective: to study the relationship between the expression of 尾 -2 Adrenergic receptor adRB2 and the clinicopathological features of prostate cancer. The potential mechanism of ADRB2 in the development of prostate cancer was investigated by in vitro cell experiment. Experimental method: 1. The expression of ADRB2 protein in normal prostate tissues and prostate cancer tissues was detected by immunohistochemistry and tissue microsequencing. To analyze the expression difference and its relationship with clinicopathological characteristics. 2. ADRB2 agonist isoproterenol and propranolol were treated with propranolol in PC-3 cells of prostate cancer. The effect of Hoechst on cell proliferation and apoptosis was detected by MTT assay and flow cytometry. Immunohistochemical method was used to detect the expression of Hedgehog signal transduction related signal factor Shhtchng Gli1 in prostate cancer, and the correlation between ADRB2 and Hedgehog signaling pathway was analyzed. PC-3 cells were treated with isoproterenol and propranolol, and the changes of Shhtchchus Gli1 were detected by real-time fluorescent quantitative PCR and Western-Blot. The result of the experiment was 1: 1. Compared with normal prostate tissues, the expression of 尾 2-adrenergic receptor was significantly increased in prostate cancer tissues, and the expression intensity of 尾 _ 2-adrenergic receptor was correlated with the pathological grade and clinical stage of prostate cancer. Isoproterenol, a 尾 2 adrenoceptor agonist, can promote the proliferation of prostate cancer cell line PC-3, and propranolol can promote the apoptosis of prostate cancer cell line PC-3, and propranolol can promote the proliferation of PC-3 cells. There was a positive correlation between the expression of ADRB2 and the expression of Ptch in prostate tissue. After treated with isoproterenol, the expression of ShhPtchngli1, a signal protein associated with Hh signaling pathway in prostate cancer cell line PC-3, was increased, and the expression of Shhtchnchngli1 in PC-3 cells was decreased after treatment with propranolol. Conclusion: sympathetic nerve may be involved in the development of prostate cancer through 尾 2-adrenergic receptor, and this effect may be related to the activation or enhancement of Hh signaling pathway.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.25

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