本文選題：子宮內(nèi)膜腫瘤　切入點：表皮生長因子　出處：《青島大學(xué)》2017年碩士論文

【摘要】：目的:研究表皮生長因子(epidermal growth factor,EGF)對子宮內(nèi)膜腺癌細胞系Ishikawa增殖的影響,并探討雌激素受體α(ERα)和Ack1激酶在其調(diào)控機制中的作用。方法:(1)無雌激素環(huán)境下,EGF和酪氨酸激酶抑制劑Dasatinib(達沙替尼)分別作用于子宮內(nèi)膜腺癌細胞系Ishikawa后,應(yīng)用CCK-8法檢測子宮內(nèi)膜腺癌細胞的增殖情況;應(yīng)用統(tǒng)計學(xué)軟件SPSS19.0進行數(shù)據(jù)分析。(2)無雌激素環(huán)境下,EGF和酪氨酸激酶抑制劑Dasatinib(達沙替尼)分別作用于子宮內(nèi)膜腺癌細胞系Ishikawa后,應(yīng)用Western blot法檢測Ishikawa細胞ERα及Ack1激酶非磷酸化與磷酸化狀態(tài)蛋白的表達情況;應(yīng)用Image J圖像分析軟件,通過磷酸化目的蛋白與非磷酸化目的蛋白條帶的吸光度值比值進行目的蛋白的相對含量分析。結(jié)果:(1)在無雌激素條件下,EGF(10μg/L)能夠促進子宮內(nèi)膜腺癌Ishikawa細胞增殖。與對照組比較有顯著性差異,P0.05。(2)達沙替尼(10 nmol/L-800 nmol/L)呈劑量依賴性抑制EGF誘導(dǎo)的子宮內(nèi)膜腺癌Ishikawa細胞增殖。與EGF處理組比較有顯著性差異,P0.05。(3)EGF能夠誘導(dǎo)Ishikawa細胞Ack1激酶及ERαTyr-537特異位點磷酸化。與對照組相比,Ack1激酶和ERαTyr-537位點的磷酸化水平升高,結(jié)果有顯著性差異,P0.05。(4)達沙替尼能夠抑制Ishikawa細胞EGF誘導(dǎo)的Ack1激酶及ERαTyr-537磷酸化。當達沙替尼濃度大于400 nmol/L時,Ack1激酶及ERαTyr-537位點磷酸化被完全抑制,與對照組比較有顯著性差異,P0.05。結(jié)論:(1)EGF促進子宮內(nèi)膜腺癌Ishikawa細胞Ack1激酶及ERαTyr-537磷酸化及促進Ishikawa細胞增殖(P0.05),EGF在子宮內(nèi)膜癌細胞發(fā)生發(fā)展作用明顯,為尋找新型抗腫瘤藥物治療靶點提供了理論基礎(chǔ)。(2)達沙替尼能夠抑制子宮內(nèi)膜腺癌Ishikawa細胞EGF誘導(dǎo)的Ack1激酶及ERαTyr-537磷酸化,并抑制Ishikawa細胞增殖(P0.05),達沙替尼可應(yīng)用于子宮內(nèi)膜癌的治療。
[Abstract]:Aim: to investigate the effects of epidermal growth factor (EGF) on the proliferation of endometrial adenocarcinoma cell line Ishikawa, and to explore the role of estrogen receptor alpha (ER 偽) and Ack1 kinase in its regulatory mechanism.Methods EGF and Dasatinib (Dasatinib), an inhibitor of tyrosine kinase, were used to detect the proliferation of endometrial adenocarcinoma cell line Ishikawa by CCK-8.Statistical software SPSS19.0 was used to analyze the data. (2) EGF and Dasatinib (Dasatinib), a tyrosine kinase inhibitor, were treated on endometrial adenocarcinoma cell line Ishikawa respectively.The expression of ER 偽 and Ack1 kinase non-phosphorylated and phosphorylated state proteins in Ishikawa cells was detected by Western blot assay, and Image J image analysis software was used.The relative content of the target protein was analyzed by the ratio of the absorbance of the phosphorylated target protein to the non-phosphorylated target protein band.Results 10 渭 g 路L ~ (-1) of Ishikawa could promote the proliferation of endometrial adenocarcinoma Ishikawa cells without estrogen.Compared with the control group, there was a significant difference (P0.05.22) Dasatinide (10 nmol/L-800 nmol / L) inhibited the proliferation of endometrial adenocarcinoma Ishikawa cells induced by EGF in a dose-dependent manner.Compared with the EGF treatment group, there was a significant difference between the two groups (P 0.05. 05. 3) EGF could induce the phosphorylation of Ack1 kinase and ER 偽 Tyr-537 specific sites in Ishikawa cells.Compared with the control group, the phosphorylation of Ack1 kinase and ER 偽 Tyr-537 sites was significantly increased. The results showed that Dasatinib could inhibit Ack1 kinase and ER 偽 Tyr-537 phosphorylation induced by EGF in Ishikawa cells.The phosphorylation of Ack1 kinase and ER 偽 Tyr-537 sites was completely inhibited when the concentration of dasatinib was more than 400 nmol/L, which was significantly different from that of the control group (P 0.05).Conclusion the Ack1 kinase and ER 偽 Tyr-537 phosphorylation of endometrial adenocarcinoma Ishikawa cells and the proliferation of Ishikawa cells can be significantly promoted by the growth of EGF in endometrial carcinoma cell line P0.05EGF may play an important role in the carcinogenesis and development of endometrial carcinoma cells.Dasatinib can inhibit Ack1 kinase and ER 偽 Tyr-537 phosphorylation induced by EGF in endometrial adenocarcinoma Ishikawa cells.The proliferation of Ishikawa cells was inhibited by P0.05, and dassatinide was used in the treatment of endometrial carcinoma.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.33

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