本文選題：子宮內(nèi)膜腫瘤　切入點(diǎn)：表皮生長(zhǎng)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(zhǎng)因子(epidermal growth factor,EGF)對(duì)子宮內(nèi)膜腺癌細(xì)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(jī)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(dá)沙替尼)分別作用于子宮內(nèi)膜腺癌細(xì)胞系Ishikawa后,應(yīng)用CCK-8法檢測(cè)子宮內(nèi)膜腺癌細(xì)胞的增殖情況;應(yīng)用統(tǒng)計(jì)學(xué)軟件SPSS19.0進(jìn)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(dá)沙替尼)分別作用于子宮內(nèi)膜腺癌細(xì)胞系Ishikawa后,應(yīng)用Western blot法檢測(cè)Ishikawa細(xì)胞ERα及Ack1激酶非磷酸化與磷酸化狀態(tài)蛋白的表達(dá)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(jìn)行目的蛋白的相對(duì)含量分析。結(jié)果:(1)在無雌激素條件下,EGF(10μg/L)能夠促進(jìn)子宮內(nèi)膜腺癌Ishikawa細(xì)胞增殖。與對(duì)照組比較有顯著性差異,P0.05。(2)達(dá)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(xì)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(xì)胞Ack1激酶及ERαTyr-537特異位點(diǎn)磷酸化。與對(duì)照組相比,Ack1激酶和ERαTyr-537位點(diǎn)的磷酸化水平升高,結(jié)果有顯著性差異,P0.05。(4)達(dá)沙替尼能夠抑制Ishikawa細(xì)胞EGF誘導(dǎo)的Ack1激酶及ERαTyr-537磷酸化。當(dāng)達(dá)沙替尼濃度大于400 nmol/L時(shí),Ack1激酶及ERαTyr-537位點(diǎn)磷酸化被完全抑制,與對(duì)照組比較有顯著性差異,P0.05。結(jié)論:(1)EGF促進(jìn)子宮內(nèi)膜腺癌Ishikawa細(xì)胞Ack1激酶及ERαTyr-537磷酸化及促進(jìn)Ishikawa細(xì)胞增殖(P0.05),EGF在子宮內(nèi)膜癌細(xì)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(diǎn)提供了理論基礎(chǔ)。(2)達(dá)沙替尼能夠抑制子宮內(nèi)膜腺癌Ishikawa細(xì)胞EGF誘導(dǎo)的Ack1激酶及ERαTyr-537磷酸化,并抑制Ishikawa細(xì)胞增殖(P0.05),達(dá)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(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.33

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 劉靜;陳悅丹;張靜;王雅杰;張勇;劉元波;;達(dá)沙替尼抑制前列腺癌細(xì)胞雄激素受體磷酸化機(jī)制研究[J];腫瘤研究與臨床;2016年06期

2 郜茜;盧永福;王昀;楊永成;蔣漢梅;;Ack-1和CDC42在胃癌組織中的表達(dá)和意義[J];青海醫(yī)學(xué)院學(xué)報(bào);2015年03期

3 楊付紅;張春娣;;肺癌的研究現(xiàn)狀[J];中國(guó)繼續(xù)醫(yī)學(xué)教育;2015年02期

4 烏力吉白乙;;老年乳腺浸潤(rùn)性癌組織中ACK1、表皮生長(zhǎng)因子受體和PTEN的表達(dá)及意義[J];中國(guó)老年學(xué)雜志;2014年06期

5 陽佳;劉壽行;劉展;;Ack1在胃癌中的表達(dá)及其臨床意義[J];湖南師范大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2014年01期

6 孫雪飛;趙暉;李揚(yáng);錢筠;白雪燕;周永建;朱紅;張勇;劉元波;;無雄激素條件下表皮生長(zhǎng)因子誘導(dǎo)前列腺癌細(xì)胞系增殖及雄激素受體磷酸化[J];基礎(chǔ)醫(yī)學(xué)與臨床;2014年03期

7 熊麗麗;田曉予;;老年人子宮頸鱗癌中ACK1和基質(zhì)金屬蛋白酶-14表達(dá)的關(guān)系[J];中國(guó)老年學(xué)雜志;2013年22期

8 李玉潔;何義富;胡冰;;達(dá)沙替尼體外抗鼻咽癌細(xì)胞增殖與轉(zhuǎn)移的作用[J];安徽醫(yī)藥;2013年10期

9 婁丙祥;計(jì)駿;蔡劬;周塵飛;石海龍;陳雪華;于穎彥;劉炳亞;張俊;朱正綱;;達(dá)沙替尼聯(lián)合奧沙利鉑協(xié)同抑制胃癌細(xì)胞增殖和遷移[J];內(nèi)科理論與實(shí)踐;2013年04期

10 王莉;王如文;蔣耀光;趙云平;龔太乾;郭偉;;Src酪氨酸激酶抑制劑dasatinib對(duì)人食管鱗癌細(xì)胞KYSE180生長(zhǎng)及凋亡的影響[J];腫瘤;2012年07期

，

本文編號(hào)：1705373