本文選題：卵巢癌　切入點(diǎn)：GOLPH3　出處：《泰山醫(yī)學(xué)院》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景 卵巢癌（ovarian carcinoma，OC）是女性生殖系統(tǒng)常見的惡性腫瘤，早期不易發(fā)現(xiàn)，一旦發(fā)現(xiàn)常常已屬晚期。上皮性卵巢癌（Epithelial Ovarian Cancer, EOC)是卵巢癌中最常見的一種類型，是婦科腫瘤中死亡率最高的一種類型。目前卵巢癌的常規(guī)治療仍然是手術(shù)、化療、放療和內(nèi)分泌治療等措施，但這些治療方法都存在著療效不佳的問題。隨著分子生物學(xué)的發(fā)展，腫瘤分子的靶向治療成為眾多學(xué)者關(guān)注的熱點(diǎn)，，基因干擾技術(shù)正逐步用于目的基因及相關(guān)基因的作用機(jī)制的研究。高爾基體磷蛋白3（GOLPH3）是近年來發(fā)現(xiàn)的一種癌基因，在多種實(shí)體腫瘤中存在過表達(dá)，并與腫瘤的臨床分期、腫瘤病理分級(jí)及轉(zhuǎn)移侵襲密切相關(guān)。GOLPH3在多種生物學(xué)過程中發(fā)揮作用，參與多種惡性腫瘤的發(fā)展過程，其高表達(dá)多與不良的臨床預(yù)后有關(guān)，而GOLPH3 在卵巢癌的發(fā)生、發(fā)展中的作用機(jī)制目前還不清楚。 目的 本課題旨在研究GOLPH3在卵巢漿液性囊腺癌組織中的表達(dá)及其與臨床病理特征之間的關(guān)系，并利用基因干擾技術(shù)初步探討GOLPH3在卵巢癌細(xì)胞生物學(xué)行為方面的的作用機(jī)制，闡明GOLPH3在卵巢癌發(fā)生、發(fā)展過程中的作用。 方法 1.應(yīng)用實(shí)時(shí)熒光定量PCR、蛋白印記法(Western blot)分別檢測(cè)各組織標(biāo)本中GOLPH3在mRNA和蛋白水平的表達(dá)，并與患者臨床病理特征進(jìn)行相關(guān)性分析。 2.構(gòu)建針對(duì)人GOLPH3基因的shRNA表達(dá)質(zhì)粒（GOLPH3-shRNA），轉(zhuǎn)染人卵巢癌SW626細(xì)胞系，使GOLPH3基因沉默。 3.利用CCK-8、細(xì)胞克隆形成實(shí)驗(yàn)及Transwell小室法檢測(cè)GOLPH3-shRNA轉(zhuǎn)染后對(duì)SW626細(xì)胞增殖、遷移及侵襲能力的影響。 結(jié)果 1.GOLPH3mRNA在卵巢漿液性囊腺癌組織中的表達(dá)高于卵巢囊腺瘤組（2.33-7.34倍），差異具有統(tǒng)計(jì)學(xué)意義（P＜0.05）。GOLPH3蛋白在卵巢漿液性囊腺癌組織中陽性表達(dá)率（73.8%）明顯高于卵巢囊腺瘤組（35.71%）（P＜0.01），差異具有統(tǒng)計(jì)學(xué)意義。 2.GOLPH3蛋白陽性表達(dá)與漿液性囊腺癌的臨床分期(p=0.019)、病理分級(jí)(p=0.042)及有無淋巴結(jié)轉(zhuǎn)移(p=0.000)有關(guān)，而與患者的年齡（p=0.881）無關(guān)（P0.05）；并且腫瘤細(xì)胞的分化程度越低其GOLPH3蛋白表達(dá)量越高（P＜0.01），差異具有統(tǒng)計(jì)學(xué)意義。 3.細(xì)胞實(shí)驗(yàn)中干擾質(zhì)粒轉(zhuǎn)染48小時(shí)后SW626細(xì)胞的轉(zhuǎn)染效率約為75%，干擾組的GOLPH3的mRNA及蛋白表達(dá)水平的表達(dá)均明顯下調(diào)(P 0.01)，差異具有統(tǒng)計(jì)學(xué)意義。 4.干擾組腫瘤細(xì)胞的增殖能力受抑制(P 0.01)，且這種抑制作用與時(shí)間無關(guān)；卵巢癌腫瘤細(xì)胞的克隆形成能力降低(P 0.01)；卵巢癌腫瘤細(xì)胞的轉(zhuǎn)移及侵襲能力亦明顯降低(P 0.01)，差異具有統(tǒng)計(jì)學(xué)意義。 結(jié)論 1．GOLPH3在卵巢漿液性囊腺癌的發(fā)生、發(fā)展中發(fā)揮著重要的作用。 2．GOLPG3促進(jìn)卵巢癌的增殖、生長(zhǎng)、遷移及侵襲，有可能成為卵巢癌治療新的靶基因。
[Abstract]:Background. Ovarian carcinoma carcinoma OCis a common malignant tumor in the female reproductive system. It is not easy to detect early, and is often late once found. Epithelial ovarian cancer Epithelial Ovarian carcinoma (EOC) is the most common type of ovarian cancer. It is one of the highest mortality rates among gynecological tumors. At present, conventional treatment for ovarian cancer is still surgery, chemotherapy, radiotherapy and endocrine therapy. With the development of molecular biology, the targeted therapy of tumor molecules has become the focus of attention of many scholars. Gene interference technique is gradually being used to study the action mechanism of target gene and related gene. Golgi body phosphoprotein 3 (Golgi) is a kind of oncogene found in recent years, which is overexpressed in many solid tumors and is associated with the clinical stage of tumor. GOLPH3 plays a role in many biological processes and participates in the development of many kinds of malignant tumors. The high expression of GOLPH3 is related to the poor clinical prognosis. The mechanisms underlying the development of ovarian cancer are unclear. Purpose. The purpose of this study was to investigate the expression of GOLPH3 in ovarian serous cystadenocarcinoma and its relationship with clinicopathological features, and to explore the role of GOLPH3 in the biological behavior of ovarian cancer cells by gene interference technique. To elucidate the role of GOLPH3 in the genesis and development of ovarian cancer. Method. 1. The expression of GOLPH3 in mRNA and protein was detected by real-time fluorescence quantitative PCR and Western blot, and the correlation was analyzed with the clinicopathological features of the patients. 2. The shRNA expression plasmid of human GOLPH3 gene was constructed and transfected into human ovarian cancer SW626 cell line. The GOLPH3 gene was silenced. 3. The effects of GOLPH3-shRNA transfection on the proliferation, migration and invasion of SW626 cells were detected by CCK-8, cell clone formation assay and Transwell chamber assay. Results. 1. The expression of GOLPH3 mRNA in ovarian serous cystadenocarcinoma was 2.33-7.34 times higher than that in ovarian cystadenoma (P < 0.05). The positive expression rate of GOLPH3 protein in ovarian serous cystadenocarcinoma was significantly higher than that in ovarian cystadenoma (35.71, P < 0.01, P < 0.01), and the positive expression rate of GOLPH3 protein in ovarian serous cystadenocarcinoma was significantly higher than that in ovarian cystadenoma (P < 0.05). It has statistical significance. 2. The positive expression of GOLPH3 protein was related to the clinical stage of serous cystadenocarcinoma, p0. 019, pathological grade p0. 042) and lymph node metastasis (p0. 000). And the lower the differentiation degree of tumor cells, the higher the expression of GOLPH3 protein (P < 0.01). 3. In the cell experiment, the transfection efficiency of SW626 cells was about 75 after 48 hours of interference plasmid transfection. The expression of mRNA and protein of GOLPH3 in the interference group was significantly down-regulated (P 0.01), and the difference was statistically significant. 4. The proliferation ability of tumor cells in the interference group was inhibited by P0.01, and the inhibitory effect was not related to time. The clone forming ability of ovarian cancer cells decreased P 0.01, and the metastasis and invasion ability of ovarian cancer cells decreased significantly (P 0.01), the difference was statistically significant. Conclusion. GOLPH3 plays an important role in the development of ovarian serous cystadenocarcinoma. 2. GOLPG3 promotes the proliferation, growth, migration and invasion of ovarian cancer and may become a new target gene for ovarian cancer therapy.
【學(xué)位授予單位】：泰山醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.31

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