【摘要】：目的:1.探討Sox2、Sall4、Klf4和β-catenin在不同宮內(nèi)膜組織中的表達(dá)及其臨床意義,并分析幾者在子宮內(nèi)膜樣腺癌組織中表達(dá)的相關(guān)性,為進(jìn)一步探討子宮內(nèi)膜癌發(fā)生機(jī)制提供理論依據(jù)。2.探索Sox2、Sall4、Klf4和β-catenin與子宮內(nèi)膜樣腺癌臨床病理特征的關(guān)系,為該腫瘤早期的診斷、治療及預(yù)后監(jiān)測(cè)提供較好的理論基礎(chǔ)。3.通過(guò)細(xì)胞學(xué)實(shí)驗(yàn),觀察經(jīng)紫杉醇處理前后Sox2、Sall4、Klf4和β-catenin在細(xì)胞株(Ishikawa細(xì)胞和HEC-1A細(xì)胞)表達(dá)情況的變化,探討紫杉醇藥物對(duì)子宮內(nèi)膜樣腺癌的化療效果,為該腫瘤進(jìn)一步靶向治療提供理論依據(jù)。方法:1.收集宮內(nèi)膜組織140例,分別為正常增生期子宮內(nèi)膜30例,增生性子宮內(nèi)膜40例(不伴不典型性的增生和不典型增生各20例),子宮內(nèi)膜樣腺癌70例(高分化癌30例,中、低分化癌各20例)。采用免疫組織化學(xué)MaxVisionTM法檢測(cè)Sox2、Sall4、Klf4與β-catenin表達(dá)水平。2.采用CCK-8檢測(cè)不同濃度紫杉醇作用于Ishikawa、HEC-1A細(xì)胞后細(xì)胞的增殖抑制率。3.Western blot方法檢測(cè)藥物作用前后Sox2、Sall4、Klf4和β-catenin表達(dá)水平變化,探討紫杉醇藥物對(duì)子宮內(nèi)膜樣腺癌的療效。4.統(tǒng)計(jì)學(xué)方法:應(yīng)用SPSS19.0軟件對(duì)實(shí)驗(yàn)結(jié)果數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析,視P0.05為具有統(tǒng)計(jì)學(xué)差異。結(jié)果:1.在正常組織及增生性子宮內(nèi)膜組織中Sox2、Sall4、Klf4基本不表達(dá),β-catenin于宮內(nèi)膜腺體細(xì)胞膜上高表達(dá),sox2、sall4、klf4與β-catenin在正常子宮內(nèi)膜與增生性子宮內(nèi)膜中的表達(dá)無(wú)明顯差異(p0.05)。同正常子宮內(nèi)膜和增生性子宮內(nèi)膜相比,子宮內(nèi)膜樣腺癌組織中sox2、sall4、klf4表達(dá)升高,β-catenin表達(dá)降低,差異具有統(tǒng)計(jì)學(xué)意義(p均小于0.05)。2.sox2、sall4、klf4與β-catenin的表達(dá)與子宮內(nèi)膜樣腺癌的病理組織學(xué)分級(jí)、浸潤(rùn)深度及淋巴結(jié)轉(zhuǎn)移有關(guān)(p0.05),但與患者年齡無(wú)關(guān)(p0.05)。3.sox2、sall4、klf4三者分別與β-catenin在子宮內(nèi)膜樣腺癌中的表達(dá)呈負(fù)相關(guān)(β-catenin與sox2:r=-0.685,p0.05;β-catenin與sall4:r=-0.453,p0.05;β-catenin與klf4:r=-0.438,p0.05),sox2、sall4、klf4三者相互之間的表達(dá)均呈正相關(guān)(sox2與sall4:r=0.456,p0.05;sox2與klf4:r=0.470,p0.05;sall4與klf4:r=0.578,p0.05)。4.1μg/ml、5μg/ml、10μg/ml、20μg/ml、100μg/ml濃度紫杉醇對(duì)ishikawa和hec-1a細(xì)胞均有明顯抑制作用,濃度越高抑制率越高。5.westernblot檢測(cè)結(jié)果發(fā)現(xiàn)ishikawa、hec-1a細(xì)胞中sox2、sall4、klf4在紫杉醇作用后表達(dá)均明顯升高,β-catenin的表達(dá)在紫杉醇作用前后無(wú)明顯變化。結(jié)論:1.sox2、sall4、klf4與β-catenin的表達(dá)與子宮內(nèi)膜樣腺癌密切相關(guān),是腫瘤相關(guān)因子。2.sox2、sall4、klf4與β-catenin表達(dá)水平與子宮內(nèi)膜樣腺癌臨床病理因素密切相關(guān),提示它們參與誘導(dǎo)子宮內(nèi)膜樣腺癌的發(fā)生發(fā)展,其表達(dá)情況可為該腫瘤的治療方法的選擇和有效的預(yù)后監(jiān)測(cè)提供有效依據(jù)。3.Sox2、Sall4、Klf4及β-catenin在子宮內(nèi)膜樣腺癌中的表達(dá)高度相關(guān),提示Sox2、Sall4、Klf4三者存在相互作用,可能是該腫瘤的腫瘤干細(xì)胞因子,并與Wnt/β-catenin信號(hào)通路相關(guān),共同推動(dòng)子宮內(nèi)膜樣腺癌的發(fā)生發(fā)展。4.單用紫杉醇β-catenin表達(dá)無(wú)變化,Sox2、Sall4、Klf4三者表達(dá)水平反而升高,推測(cè)細(xì)胞可能產(chǎn)生耐藥性,單用化療藥物對(duì)子宮內(nèi)膜樣腺癌治療效果可能不佳,易出現(xiàn)腫瘤復(fù)發(fā)和轉(zhuǎn)移。
[Abstract]:Objective:1. The expression and clinical significance of Sox2, Sall4, Klf4 and Catenin in different endometrial tissues were discussed. The correlation between the expression of Sox 2, Sall4, Klf4 and Catenin in the tissue of endometrial adenocarcinoma was analyzed, and the theoretical basis for further study of the mechanism of endometrial carcinoma was also discussed. To explore the relationship between Sox2, Sall4, Klf4 and the clinicopathological features of endometrial-like adenocarcinoma, and provide a good theoretical basis for the early diagnosis, treatment and prognosis of the tumor. The changes of the expression of Sox2, Sall4, Klf4 and Catenin in cell lines (Ishikawa cells and HEC-1A cells) before and after the treatment with paclitaxel were observed by the cytological experiments, and the effect of the paclitaxel drug on the endometrial adenocarcinoma was discussed, and the theoretical basis for further targeted therapy of the tumor was also discussed. Method:1. 140 cases of endometrial tissue were collected, including 30 cases of normal proliferative endometrium,40 cases of hyperplastic endometrium (20 cases of atypical hyperplasia and atypical hyperplasia),70 cases of endometrial adenocarcinoma (30 cases of high differentiation cancer,20 cases of medium and low differentiated cancer). The expression level of Sox2, Sall4, Klf4 and HCO3-catenin was detected by using the immunohistochemical method of MaxVisionTM. The effect of paclitaxel on endometrial adenocarcinoma was studied by using CCK-8 to detect the inhibitory rate of paclitaxel on the cells after Ishikawa and HEC-1A cells. Statistical method: SPSS 19.0 software was used to carry out the statistical analysis of the data of the experiment, and the statistical difference was observed according to the P0.05. Results:1. The expression of Sox 2, Sall4 and Klf4 in the normal tissues and the hyperplastic endometrial tissues was not significant, and the expression of sox2, sall4, klf4 in the normal endometrium and the proliferative endometrium was not significantly different (p0.05). In comparison with that normal endometrium and the proliferative endometrium, the expression of sox2, sall4, klf4 in the tissue of the endometrial-like adenocarcinoma was increased, the expression of HCO3-catinin was decreased, and the difference was statistically significant (p <0.05). The expression of klf4 and n-catenin was related to the pathological grade, invasion depth and lymph node metastasis (p0.05), but not related to the age of the patient (p0.05).3. sox2, sall4, and klf4 were negatively correlated with the expression of n-catenin in the endometrioid adenocarcinoma (P-catenin and sox2: r =-0.685, p0.05; The expression of HCO3-catenin and sall4: r =-0.453, p0.05; t-catenin and klf4: r =-0.438, p0.05), sox2, sall4, and klf4 were positively correlated with each other (sox2 and sall4: r = 0.456, p0.05; splay 4 and klf4: r = 0.470, p0.05). 4.1. mu.g/ ml,5. mu.g/ ml,10. mu.g/ ml,20. mu.g/ ml, The results of western blot showed that the expression of sox2, sall4 and klf4 in shikawa and hc-1a cells increased significantly after the effect of paclitaxel. Conclusion:1. The expression of sox2, sall4, klf4 and n-catenin is closely related to the endometrial adenocarcinoma, and it is a tumor-related factor. the expression condition can provide an effective basis for the selection of the treatment method of the tumor and the effective prognosis monitoring,3. the expression level of the Sox2, the Sall4, the Klf4 and the n-catenin in the endometrial-like adenocarcinoma is highly correlated, and the interaction of the Sox 2, the Sall4 and the Klf4 can be the tumor stem cell factor of the tumor, It is associated with the Wnt/ P-cattenin signaling pathway to promote the development of endometrial-like adenocarcinoma. The expression of Taxol-catenin alone increased, and the expression level of Sox2, Sall4 and Klf4 increased, and it was suggested that the cell might be resistant to drug resistance. The effect of chemotherapy alone on the treatment of endometrial-like adenocarcinoma may not be good, and the recurrence and metastasis of the tumor can be easily.
【學(xué)位授予單位】：川北醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R737.33

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