本文選題：舌鱗狀細(xì)胞癌 + 鞘氨醇激酶1　； 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：研究目的:檢測鞘氨醇激酶1(sphingosine kinase 1,Sph K1)在舌鱗狀細(xì)胞癌(tongue squamous cell carcinoma,TSCC)中的表達(dá)及其與臨床病理特征和淋巴管生成之間的關(guān)系,并探索其在舌鱗狀細(xì)胞癌發(fā)生發(fā)展中的作用及可能的分子機(jī)制。研究方法:1.收集天津市口腔醫(yī)院50例舌鱗狀細(xì)胞癌手術(shù)標(biāo)本作為研究對(duì)象,應(yīng)用免疫組化法,檢測Sph K1蛋白的表達(dá)水平以及淋巴管密度(lymphatic vessel density,LVD),并分析Sph K1蛋白的表達(dá)水平與臨床病理特征及淋巴管生成間的關(guān)系;2.體外實(shí)驗(yàn)使用Sph K1抑制劑N,N-二甲基鞘氨醇(N,N-dimethylsphingosine,DMS)干預(yù)Tca8113P160舌鱗狀細(xì)胞癌細(xì)胞系,CCK-8法檢測DMS對(duì)細(xì)胞增殖的影響,Transwell小室模型檢測DMS對(duì)細(xì)胞遷移和侵襲能力的影響,Western blot檢測DMS對(duì)Sph K1、FAK、p-FAK、E-cadherin和N-cadherin蛋白表達(dá)的影響;另外用FAK抑制劑PF573228干預(yù)Tca8113P160舌鱗狀細(xì)胞癌細(xì)胞系,CCK-8法檢測PF573228對(duì)細(xì)胞增殖的影響,Transwell小室模型檢測PF573228對(duì)細(xì)胞遷移和侵襲能力的影響,Western blot檢測PF573228對(duì)E-cadherin和N-cadherin蛋白表達(dá)的影響。研究結(jié)果:1.Sph K1在舌鱗狀細(xì)胞癌組織中陽性表達(dá)率(62.0%)明顯高于白斑(42.9%)、正常舌粘膜組織(0%),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。Sph K1表達(dá)水平與患者的臨床分期(P=0.002)、有無淋巴結(jié)轉(zhuǎn)移(P=0.001)、T分期(P=0.019)及組織學(xué)分級(jí)(P=0.024)密切相關(guān),與患者的性別(P=0.341)、年齡(P=0.786)、吸煙情況(P=0.547)及飲酒情況(P=0.566)無顯著相關(guān)性(P0.05);淋巴結(jié)轉(zhuǎn)移陽性組LVD(10.76±3.33)明顯高于淋巴結(jié)轉(zhuǎn)移陰性組LVD(7.84±2.53),差異有統(tǒng)計(jì)學(xué)意義(P0.05);Sph K1高表達(dá)組LVD(10.81±2.86)明顯高于Sph K1低表達(dá)組LVD(6.84±2.32),差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2.DMS和PF573228均能抑制Tca8113P160細(xì)胞的增殖,呈時(shí)間和劑量依賴性;DMS和PF573228均能抑制細(xì)胞的遷移和侵襲能力(P0.05);Western blot結(jié)果顯示DMS抑制Sph K1蛋白的表達(dá),同時(shí)下調(diào)FAK、p-FAK、N-cadherin蛋白的表達(dá),上調(diào)E-cadherin蛋白的表達(dá)(P0.05),PF573228下調(diào)N-cadherin蛋白的表達(dá),上調(diào)E-cadherin蛋白的表達(dá)(P0.05)。結(jié)論:1.Sph K1與舌鱗狀細(xì)胞癌的發(fā)生發(fā)展及轉(zhuǎn)移密切相關(guān),可能通過促進(jìn)腫瘤淋巴管生成影響舌鱗狀細(xì)胞癌頸淋巴結(jié)轉(zhuǎn)移。2.Sph K1通過FAK通路調(diào)控上皮間質(zhì)轉(zhuǎn)化(epithelial-mesenchymal transition,EMT)進(jìn)而影響Tca8113P160舌鱗狀細(xì)胞癌細(xì)胞的遷移和侵襲。
[Abstract]:Objective: to detect the expression of sphingosine kinase (1(sphingosine kinase 1) in tongue squamous cell carcinoma (TSCC) and its relationship with clinicopathological features and lymphangiogenesis.To explore its role in the development of squamous cell carcinoma of tongue and its possible molecular mechanism.Research method: 1.Fifty cases of squamous cell carcinoma of tongue were collected from Tianjin Stomatology Hospital.The expression level of Sph K1 protein and lymphatic vessel density were detected. The relationship between the expression level of Sph K1 protein and clinicopathological features and lymphangiogenesis was analyzed.To influence the expression of E-cadherin and N-cadherin protein in Sph K1FAKP p-FAKT.In addition, FAK inhibitor PF573228 was used to detect the effect of PF573228 on cell proliferation in Tca8113P160 squamous cell carcinoma cell line (Tca8113P160) by CCK-8 method. Transwell chamber model was used to detect the effect of PF573228 on cell migration and invasion. Western blot was used to detect the effect of PF573228 on the expression of E-cadherin and N-cadherin protein.P0. 019) and histologic grading P0. 024) were closely related.In K1 low expression group, LVD(6.84 鹵2.32, the difference was statistically significant (P 0.05). 2. DMS and PF573228 could inhibit the proliferation of Tca8113P160 cells.In a time-and dose-dependent manner, both DMS and PF573228 could inhibit cell migration and invasion. The results of Western blot showed that DMS inhibited the expression of Sph K1 protein, down-regulated the expression of FAK-p-FAK-N-cadherin protein, up-regulated the expression of E-cadherin protein and down-regulated the expression of N-cadherin protein.The expression of E-cadherin protein was up-regulated.Conclusion: 1. SphK1 is closely related to the occurrence, development and metastasis of tongue squamous cell carcinoma.SphK1 may affect the cervical lymph node metastasis of tongue squamous cell carcinoma by promoting lymphangiogenesis. 2. SphK1 regulates epithelial mesenchymal transition via FAK pathway and then affects the migration and invasion of Tca8113P160 squamous cell carcinoma.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R739.86

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