【摘要】：研究背景:在男性泌尿生殖系統(tǒng)中,前列腺癌是常見(jiàn)的惡性腫瘤。隨著社會(huì)的的發(fā)展,人口老齡化及生活習(xí)慣等發(fā)生改變,包括中國(guó)在內(nèi)的亞洲地區(qū),前列腺癌發(fā)病率呈逐年上升趨勢(shì),已位居該地區(qū)泌尿系腫瘤的第二位。目前研究已經(jīng)提示前列腺癌發(fā)生及發(fā)展的病理進(jìn)程與雄激素受體(AR)密切相關(guān),前列腺癌細(xì)胞惡性程度增加,其雄激素受體的表達(dá)減少;早期前列腺癌組織中雄激素受體的表達(dá)高于晚期,高度及中度分化的前列腺癌組織中雄激素受體的表達(dá)高于低分化前列腺癌。研究發(fā)現(xiàn)上皮來(lái)源的惡性腫瘤細(xì)胞可分泌免疫球蛋白G(IgG),并具有促進(jìn)腫瘤細(xì)胞生長(zhǎng)、遷移的作用。在前期研究中,我們發(fā)現(xiàn)前列腺癌中表達(dá)IgG,其表達(dá)隨著前列腺癌惡性程度增加而增高,提示IgG可能在前列腺癌發(fā)病過(guò)程中起重要作用。那么,前列腺癌AR與IgG之間是否存在相關(guān)性及其作用機(jī)制?目前國(guó)內(nèi)外尚未有相關(guān)研究報(bào)道。我們擬通過(guò)干預(yù)前列腺癌細(xì)胞株中AR的表達(dá),檢測(cè)IgG表達(dá)及前列腺癌細(xì)胞增殖、遷移等生物學(xué)特性的變化,明確前列腺癌AR與IgG之間關(guān)系。研究目的:研究調(diào)控前列腺癌細(xì)胞中AR對(duì)IgG表達(dá)的影響,及對(duì)前列腺癌細(xì)胞增殖、遷移的作用。研究方法:(1)Western blot分別檢測(cè)雄激素依賴(lài)性前列腺癌細(xì)胞株LNCap細(xì)胞及去勢(shì)抵抗性前列腺癌細(xì)胞株P(guān)C-3細(xì)胞中AR及IgG蛋白的表達(dá)。(2)構(gòu)建細(xì)胞模型AR基因(pCDNA3.1+)轉(zhuǎn)染PC-3構(gòu)建AR過(guò)表達(dá)的PC-3-AR細(xì)胞,沉默LNCap中AR基因表達(dá)構(gòu)建LNCap-siAR細(xì)胞。(3)檢測(cè)相關(guān)指標(biāo)Western blot檢測(cè)AR及IgG表達(dá)量;Q-PCR檢測(cè)細(xì)胞株中IgG mRNA表達(dá)量;四氮甲基唑氮(MTT)、細(xì)胞劃痕方法檢測(cè)細(xì)胞的增殖及遷移能力。(4)統(tǒng)計(jì)學(xué)方法采用SPSS20.0統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)處理,數(shù)據(jù)用x± s表示,PC-3,PC-3-V,PC-3-AR 及 LNCap,LNCap-siCon,LNCap-siAR 多組細(xì)胞間 IgG mRNA 及蛋白表達(dá)量采用單因素方差分析(采用Bonferroni方法),檢驗(yàn)水準(zhǔn)α= 0.05。研究結(jié)果:(1)LNCap細(xì)胞與PC-3細(xì)胞相比較,AR高表達(dá),IgG低表達(dá)(P0.05)。(2)PC-3細(xì)胞轉(zhuǎn)染AR基因后,AR表達(dá)增高,PC-3-AR細(xì)胞較PC-3細(xì)胞低表達(dá)IgGmRNA、IgG蛋白,PC-3-AR細(xì)胞較PC-3細(xì)胞增殖、遷移能力減弱(p0.01)。LNCap細(xì)胞沉默AR基因后,AR蛋白表達(dá)降低,LNCap-siAR細(xì)胞較LNCap細(xì)胞高表達(dá)IgG mRNA及IgG蛋白,LNCap-siAR細(xì)胞較LNCap細(xì)胞增殖、遷移能力增強(qiáng)(p0.01)。研究結(jié)論:調(diào)控前列腺癌細(xì)胞AR可影響IgG蛋白的表達(dá),并使其增殖、遷移能力發(fā)生改變。上調(diào)前列腺癌細(xì)胞AR的表達(dá)可導(dǎo)致IgG低表達(dá),腫瘤細(xì)胞增殖、遷移能力減弱,腫瘤惡性程度降低。沉默前列腺癌細(xì)胞AR的表達(dá)可導(dǎo)致IgG高表達(dá),腫瘤細(xì)胞增殖、遷移能力增強(qiáng),腫瘤惡性程度增加。
[Abstract]:Background: prostate cancer is a common malignant tumor in male genitourinary system. With the development of society, the aging population and living habits have changed. In Asia, including China, the incidence of prostate cancer has been increasing year by year, and has ranked second among the urinary system tumors in this region. The present study has shown that the pathological process of the occurrence and development of prostate cancer is closely related to the androgen receptor (AR). The malignant degree of prostate cancer cell increases and the expression of androgen receptor decreases. The expression of androgen receptor in early prostate cancer was higher than that in advanced stage, and the expression of androgen receptor in highly and moderately differentiated prostate cancer was higher than that in poorly differentiated prostate cancer. It was found that epithelial malignant tumor cells secreted immunoglobulin G (IgG), and promoted the growth and migration of tumor cells. In previous studies, we found that the expression of IgG, in prostate cancer increased with the increase of the malignant degree of prostate cancer, suggesting that IgG may play an important role in the pathogenesis of prostate cancer. Is there a correlation between AR and IgG in prostate cancer and its mechanism? At present, there is no related research report at home and abroad. We intend to investigate the relationship between prostate cancer AR and IgG by interfering with the expression of AR in prostate cancer cell lines and detecting the expression of IgG and the changes of biological characteristics such as proliferation and migration of prostate cancer cells. Aim: to investigate the effects of AR on the expression of IgG and the proliferation and migration of prostate cancer cells. Methods: (1) Western blot was used to detect the expression of AR and IgG in androgen-dependent prostate cancer cell line LNCap and castrated resistant prostate cancer cell line PC-3, respectively. (2) PC-3 was transfected with AR gene (pCDNA3.1) to construct AR overexpression PC-3-AR cells. LNCap-siAR cells were constructed by silencing AR gene expression in LNCap. (3) AR and IgG expression levels were detected by Western blot and IgG mRNA expression in cell lines was detected by Q-PCR. The cell proliferation and migration were detected by (MTT), cell scratch method. (4) the data were processed by SPSS20.0 software. The expression of IgG mRNA and protein in LNCap,LNCap-siCon,LNCap-siAR and PC-3 PC-3-AR cells was expressed by x 鹵s. The expression of IgG mRNA and protein was analyzed by single factor ANOVA (Bonferroni method), and the test level was 偽 = 0.05. Results: (1) compared with PC-3 cells, LNCap cells had higher expression of AR than PC-3 cells (P0.05). (2). After transfection of AR gene, the expression of AR in PC-3-AR cells was higher than that in PC-3 cells. The proliferation of PC-3-AR cells was higher than that of PC-3 cells, and the expression of IgGmRNA,IgG protein in PC-3-AR cells was lower than that in PC-3 cells. The expression of AR protein in LNCap-siAR cells was lower than that in LNCap cells (p0.01). The expression of IgG mRNA in LNCap-siAR cells was higher than that in LNCap cells, and the proliferation of LNCap-siAR cells was higher than that of LNCap cells (p0.01), and the migration ability of LNCap-siAR cells was higher than that of LNCap cells (p0.01). Conclusion: the regulation of AR can affect the expression of IgG protein and change its proliferation and migration ability. Upregulation of AR expression in prostate cancer cells resulted in low expression of IgG, decreased proliferation and migration of tumor cells, and decreased tumor malignancy. Silencing the expression of AR in prostate cancer cells resulted in high expression of IgG, increased proliferation and migration of tumor cells, and increased malignancy of tumor cells.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R737.25

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