【摘要】：食管癌是我國(guó)最常見(jiàn)的消化道腫瘤之一。雖然隨著外科、麻醉、圍手術(shù)期處理以及重癥監(jiān)護(hù)條件和技術(shù)取得較大的提高,但是單純手術(shù)治療效果仍不理想。其原因在于食管癌發(fā)生和發(fā)展的分子機(jī)制目前仍不清楚,導(dǎo)致食管癌療效欠佳。腫瘤細(xì)胞代謝異常是腫瘤細(xì)胞顯著區(qū)別于正常細(xì)胞的顯著特征之一。從腫瘤代謝的角度尋找食管癌的治療靶點(diǎn)很可能為食管癌的治療帶來(lái)新的希望。甲羥戊酸(MVA,Mevalonate)途徑除了終產(chǎn)物膽固醇外,還能產(chǎn)生許多中間代謝產(chǎn)物,如類異戊二烯,泛醌等。這些物質(zhì)在細(xì)胞重要的生理過(guò)程中發(fā)揮作用。甲羥戊酸代謝途徑在食管鱗癌發(fā)生中的功能目前仍不清楚。在本研究中,我們克隆了甲羥戊酸代謝限速酶3-羥基-3-甲基戊二酰輔酶A還原酶(3-Hydroxy-3-methylglutaryl coenzyme A reductase,HMGCR),并對(duì)其進(jìn)行了功能和所涉機(jī)制的初步研究。在本研究中,我們收集食管鱗癌組織標(biāo)本,培養(yǎng)食管鱗癌細(xì)胞系,利用熒光定量PCR檢測(cè)食管鱗癌組織及其配對(duì)的正常組織中HMGCR的mRNA水平,利用蛋白印跡檢測(cè)食管鱗癌組織和食管鱗癌細(xì)胞中HMGCR的蛋白水平。在細(xì)胞水平上,我們通過(guò)脂質(zhì)體轉(zhuǎn)染食管鱗癌細(xì)胞,建立過(guò)表達(dá)HMGCR的食管鱗癌穩(wěn)定細(xì)胞株;設(shè)計(jì)RNA干擾序列,下調(diào)HMGCR在食管鱗癌細(xì)胞中的表達(dá)。我們利用MTT實(shí)驗(yàn)、Boyden Chamber和軟瓊脂集落實(shí)驗(yàn)分析HMGCR對(duì)食管鱗癌細(xì)胞生長(zhǎng)、遷移和克隆形成的影響;利用GST-pull down和蛋白印跡檢測(cè)HMGCR對(duì)Ras-ERK信號(hào)通路的活化作用。最后,我們?cè)谑彻荀[癌細(xì)胞中過(guò)表達(dá)或下調(diào)c-Myc的表達(dá),通過(guò)熒光定量PCR和蛋白印跡檢測(cè)c-Myc的表達(dá)對(duì)HMGCR mRNA和蛋白水平的影響。我們的研究結(jié)果顯示,與正常食管粘膜組織相比,HMGCR在食管鱗癌組織中的mRNA水平和蛋白水平均呈現(xiàn)上調(diào)趨勢(shì)。HMGCR在食管鱗癌細(xì)胞株中的表達(dá)水平高于永生化的食管粘膜上皮細(xì)胞。在食管鱗癌細(xì)胞Eca109和正常食管粘膜細(xì)胞SHEE中過(guò)表達(dá)HMGCR促進(jìn)食管鱗癌細(xì)胞生長(zhǎng)、遷移和在軟瓊脂上克隆集落;在食管鱗癌細(xì)胞Eca109和Caes-17中下調(diào)HMGCR的表達(dá)抑制食管鱗癌細(xì)胞遷移和在軟瓊脂上克隆集落。在分子機(jī)制研究中,我們發(fā)現(xiàn)hmgcr過(guò)表達(dá)促進(jìn)ras活化,上調(diào)erk磷酸化水平。在食管鱗癌細(xì)胞中,我們發(fā)現(xiàn)代謝的重要調(diào)控因子c-myc上調(diào)hmgcr的mrna水平和蛋白水平。綜上所述,我們的研究結(jié)果提供了充分的證據(jù),證明hmgcr在食管鱗癌發(fā)生發(fā)展過(guò)程中的重要功能。同時(shí),我們的研究也提示hmgcr的抑制劑他汀用于食管鱗癌治療的可能性。本研究可以分為如下三個(gè)部分:第一部分hmgcr在食管鱗癌組織和食管鱗癌細(xì)胞中表達(dá)上調(diào)目的:研究hmgcr在食管鱗癌組織及配對(duì)的正常組織、食管鱗癌細(xì)胞株中的表達(dá)模式。方法:首先利用熒光定量pcr(real-timepcr)檢測(cè)hmgcr在40例食管鱗癌組織及配對(duì)的正常組織中的mrna水平;使用蛋白印跡法,檢測(cè)隨機(jī)挑選的6例食管鱗癌組織及配對(duì)的正常組織中hmgcr的蛋白水平,驗(yàn)證熒光定量pc結(jié)果;最后,利用蛋白印跡檢測(cè)正常食管上皮細(xì)胞和食管鱗癌細(xì)胞中hmgcr的蛋白水平。結(jié)果:mrna水平的檢測(cè)結(jié)果顯示,食管鱗癌組織中hmgcr的mrna水平較配對(duì)的正常組織顯著升高;蛋白印跡實(shí)驗(yàn)結(jié)果表明,食管鱗癌組織中hmgcr的蛋白水平較配對(duì)的正常組織顯著上調(diào),這一結(jié)果與熒光定量pcr的結(jié)果一致;最后,對(duì)多種食管鱗癌細(xì)胞和正常食管上皮細(xì)胞的蛋白印跡結(jié)果顯示,hmgcr在正常食管上皮細(xì)胞中的表達(dá)水平較低,在食管鱗癌細(xì)胞中的表達(dá)水平較高。結(jié)論:在食管鱗癌組織和細(xì)胞系中,hmgcr的mrna水平和蛋白水平均有較強(qiáng)的表達(dá)。與正常組織相比較,食管鱗癌組織中hmgcr的表達(dá)水平上升;與正常食管上皮細(xì)胞相比,hmgcr在鱗癌細(xì)胞中的表達(dá)水平升高。這些結(jié)果提示hmgcr在食管鱗癌發(fā)生發(fā)展過(guò)程中很可能起著非常重要的作用。第二部分hmgcr對(duì)食管鱗癌細(xì)胞生長(zhǎng)、遷移和克隆集落的影響目的:研究hmgcr對(duì)食管鱗癌細(xì)胞惡性行為(如生長(zhǎng)、遷移、克隆集落等)的影響,揭示hmgcr在食管鱗癌進(jìn)展中的功能。方法:利用脂質(zhì)體轉(zhuǎn)染hmgcr的表達(dá)載體(myc-hmgcr,帶myc標(biāo)簽)至食管鱗癌細(xì)胞eca109和正常食管上皮細(xì)胞shee中;通過(guò)mtt法檢測(cè)hmgcr對(duì)食管鱗癌細(xì)胞eca109和正常食管上皮細(xì)胞shee生長(zhǎng)的影響;通過(guò)軟瓊脂集落法研究hmgcr對(duì)食管鱗癌細(xì)胞克隆形成能力的影響;借助于細(xì)胞遷移模型揭示hmgcr對(duì)食管鱗癌細(xì)胞eca109和正常食管上皮細(xì)胞shee遷移的影響。同時(shí),制備hmgcrrna干擾的病毒載體,在食管鱗癌細(xì)胞eca109、caes17中下調(diào)hmgcr的表達(dá);利用軟瓊脂集落法揭示下調(diào)hmgcr的表達(dá)對(duì)食管鱗癌細(xì)胞克隆形成的影響;借助細(xì)胞遷移模型研究hmgcr表達(dá)下調(diào)對(duì)食管鱗癌細(xì)胞遷移能力的影響結(jié)果:通過(guò)脂質(zhì)體介導(dǎo)的穩(wěn)定轉(zhuǎn)染,在食管鱗癌細(xì)胞eca109和正常食管上皮細(xì)胞shee中建立了穩(wěn)定表達(dá)細(xì)胞株,過(guò)表達(dá)帶myc標(biāo)簽的hmgcr。mtt實(shí)驗(yàn)結(jié)果表明,穩(wěn)定表達(dá)hmgcr促進(jìn)食管鱗癌細(xì)胞eca109、正常食管上皮細(xì)胞shee的生長(zhǎng);細(xì)胞遷移實(shí)驗(yàn)顯示,hmgcr在eca109和shee細(xì)胞中的表達(dá)增加食管鱗癌細(xì)胞的運(yùn)動(dòng)能力;軟瓊脂集落形成實(shí)驗(yàn)顯示,hmgcr在eca109細(xì)胞中的表達(dá)促進(jìn)其非錨定性生長(zhǎng)。此外,我們構(gòu)建了hmgcrrna干擾的慢病毒載體,非常有效地干擾hmgcr在食管鱗癌細(xì)胞eca109和caes17中的表達(dá)。細(xì)胞遷移實(shí)驗(yàn)表明,hmgcr表達(dá)下降削弱了食管鱗癌細(xì)胞eca109和caes17的運(yùn)動(dòng)能力;克隆集落形成實(shí)驗(yàn)顯示,干擾hmgcr的表達(dá)使食管鱗癌細(xì)胞的非錨定性生長(zhǎng)的能力受到抑制。結(jié)論:hmgcr促進(jìn)食管鱗癌細(xì)胞的生長(zhǎng)、遷移、克隆形成能力,干擾hmgcr的表達(dá)抑制食管鱗癌細(xì)胞非錨定性生長(zhǎng)和遷移。hmgcr對(duì)食管鱗癌的進(jìn)展發(fā)揮促進(jìn)作用。第三部分hmgcr在食管鱗癌細(xì)胞中激活ras-erk信號(hào)通路目的:研究hmgcr調(diào)控食管鱗癌細(xì)胞惡性行為(如生長(zhǎng)、遷移和克隆集落)的分子機(jī)制。方法:利用gst-pulldown平臺(tái),研究hmgcr的表達(dá)ras的活化作用及對(duì)erk磷酸化水平的影響;通過(guò)熒光定量pcr和蛋白印跡,檢測(cè)c-myc基因的表達(dá)對(duì)hmgcr的mrna水平和蛋白水平的影響。結(jié)果:GST-pull down分析顯示,過(guò)表達(dá)HMGCR促進(jìn)Ras的活化,上調(diào)ERK的磷酸化水平。干擾HMGCR的表達(dá)抑制ERK的磷酸化。熒光定量PCR和蛋白印跡的實(shí)驗(yàn)結(jié)果顯示,過(guò)表達(dá)c-Myc上調(diào)HMGCR的mRNA水平和蛋白水平,干擾cMyc的表達(dá)抑制HMGCR的mRNA水平和蛋白水平。結(jié)論:HMGCR在食管鱗癌細(xì)胞中激活Ras-ERK信號(hào)通路,代謝調(diào)控的關(guān)鍵分子c-Myc調(diào)控HMGCR的表達(dá)。
[Abstract]:Esophageal cancer is one of the most common gastrointestinal tumors in China. Although the surgical, anesthesia, perioperative management and intensive care conditions and techniques have been greatly improved, the effect of surgical treatment alone is still unsatisfactory. Abnormal metabolism of tumor cells is one of the significant characteristics that distinguish tumor cells from normal cells. Looking for therapeutic targets for esophageal cancer from the perspective of tumor metabolism may bring new hope for the treatment of esophageal cancer. Diene, ubiquinone and so on. These substances play an important role in the physiological process of cells. The function of mevalonate pathway in esophageal squamous cell carcinogenesis is still unclear. In this study, we cloned the mevalonate metabolic rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (3-Hydroxy-3-methylglutaryl coenzyme A reductase) In this study, we collected esophageal squamous cell carcinoma tissue samples, cultured esophageal squamous cell carcinoma cell lines, detected the mRNA level of HMGCR in esophageal squamous cell carcinoma tissues and their matched normal tissues by fluorescence quantitative PCR, and detected esophageal squamous cell carcinoma tissues and esophageal squamous cell carcinoma fine by Western blot. Protein level of HMGCR in esophageal squamous cell carcinoma cells. At the cellular level, we established a stable cell line of esophageal squamous cell carcinoma overexpressing HMGCR by liposome transfection. RNA interference sequence was designed to down-regulate the expression of HMGCR in esophageal squamous cell carcinoma cells. The effect of HMGCR on Ras-ERK signaling pathway was detected by GST-pull down and Western blotting. Finally, we overexpressed or down-regulated the expression of c-Myc in esophageal squamous cell carcinoma cells, and detected the effect of c-Myc expression on HMGCR mRNA and protein levels by fluorescence quantitative PCR and Western blotting. The results showed that HMGCR was up-regulated in both mRNA and protein levels in esophageal squamous cell carcinoma compared with normal esophageal mucosa. The expression level of HMGCR in esophageal squamous cell carcinoma cell lines was higher than that in immortalized esophageal epithelial cells. Promote the growth, migration and cloning of esophageal squamous cell carcinoma cells on soft agar; down-regulate the expression of HMGCR in esophageal squamous cell carcinoma cells Eca109 and Caes-17, inhibit the migration of esophageal squamous cell carcinoma cells and clone colonies on soft agar. In the study of molecular mechanism, we found that overexpression of HMGCR promoted Ras activation and up-regulated ERK phosphorylation. In conclusion, our findings provide sufficient evidence to support the important role of HMGCR in the development of esophageal squamous cell carcinoma. Our findings also suggest that statin, an inhibitor of hmgcr, may be useful in the treatment of esophageal squamous cell carcinoma. This study can be divided into the following three parts: the first part is the up-regulation of HMGCR expression in esophageal squamous cell carcinoma and esophageal squamous cell carcinoma. The protein levels of HMGCR in 6 randomly selected esophageal squamous cell carcinoma tissues and matched normal tissues were detected by Western blot to verify the results of quantitative fluorescence PC. Finally, the protein levels of HMGCR in normal esophageal epithelial cells and esophageal squamous cell carcinoma cells were detected by Western blot. The results of Western blotting showed that the protein level of HMGCR in esophageal squamous cell carcinoma was significantly higher than that in matched normal tissues, which was consistent with the results of fluorescence quantitative pcr. Western blot analysis showed that the expression of HMGCR was lower in normal esophageal epithelial cells and higher in esophageal squamous cell carcinoma cells. Conclusion: The expression of HMGCR in esophageal squamous cell carcinoma tissue and cell line was higher than that in normal esophageal tissue. These results suggest that the expression of HMGCR may play an important role in the development of esophageal squamous cell carcinoma. Part two: The effects of HMGCR on the growth, migration and cloning of esophageal squamous cell carcinoma cells. The effect of Cr on malignant behavior of esophageal squamous cell carcinoma cells (e.g. growth, migration, colony cloning, etc.) and the function of HMGCR in the progression of esophageal squamous cell carcinoma were revealed. The effects of HMGCR on the growth of esophageal epithelial cells ECA 109 and normal esophageal epithelial cells shee; the effects of HMGCR on the clonal formation of esophageal squamous cell carcinoma cells were studied by soft agar colony assay; the effects of HMGCR on the migration of esophageal squamous cell carcinoma cells ECA 109 and normal esophageal epithelial cells shee were revealed by cell migration model. The expression of HMGCR was down-regulated in esophageal squamous cell carcinoma cells Eca109 and caes17; the effect of down-regulated expression of HMGCR on the formation of esophageal squamous cell carcinoma cell clones was revealed by soft agar colony assay; the effect of down-regulated expression of HMGCR on the migration ability of esophageal squamous cell carcinoma cells was studied by cell migration model; the results showed that stable transfection mediated by liposome could induce fine esophageal squamous cell carcinoma cells. A stable expression cell line was established in Eca109 cells and normal esophageal epithelial cells shee. over-expression of myc-tagged hmgcr. MTT assay showed that stable expression of HMGCR promoted the growth of esophageal squamous cell carcinoma cell Eca109 and normal esophageal epithelial cells shee. cell migration assay showed that the expression of HMGCR in Eca109 and shee cells increased the fineness of esophageal squamous cell carcinoma. In addition, we constructed a lentiviral vector interfered by hmgcrrna, which was very effective in interfering with the expression of HMGCR in esophageal squamous cell carcinoma cells ECA 109 and caes17. Cell migration assay showed that the decrease of HMGCR expression weakened the expression of caes17 and ECA 109 cells. The motility of esophageal squamous cell carcinoma cells Eca109 and caes17 was inhibited by interfering with the expression of hmgcr. conclusion: HMGCR can promote the growth, migration and clonal formation of esophageal squamous cell carcinoma cells, and interfere with the expression of HMGCR can inhibit the Non-anchoring growth and Non-anchoring growth of esophageal squamous cell carcinoma cells. The third part is the activation of ras-erk signaling pathway by HMGCR in esophageal squamous cell carcinoma cells. Objective: To study the molecular mechanism of HMGCR in regulating malignant behavior of esophageal squamous cell carcinoma cells (such as growth, migration and clonal colony). Results: GST-pull down analysis showed that over-expression of HMGCR promoted the activation of Ras and up-regulated the phosphorylation level of ERK. Interference of HMGCR expression inhibited the phosphorylation of ERK. The results of Western blotting showed that overexpression of c-Myc up-regulated the mRNA and protein levels of HMGCR, interfered with the expression of cMyc and inhibited the mRNA and protein levels of HMGCR. Conclusion: HMGCR activates Ras-ERK signaling pathway in esophageal squamous cell carcinoma cells, and c-Myc, the key molecule of metabolic regulation, regulated the expression of HMGCR.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R735.1

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 洪順家;婦科鱗癌細(xì)胞中甲狀旁腺激素相關(guān)蛋白的表達(dá)[J];國(guó)外醫(yī)學(xué).婦產(chǎn)科學(xué)分冊(cè);1994年05期

2 陳晨;甲狀旁腺激素相關(guān)蛋白在婦科鱗癌細(xì)胞中的表達(dá)[J];國(guó)外醫(yī)學(xué).婦產(chǎn)科學(xué)分冊(cè);1995年01期

3 陳主初，邵細(xì)蕓;大鼠鼻腔鱗癌細(xì)胞系建立及其特性[J];癌變.畸變.突變;1995年04期

4 唐利;劉博強(qiáng);簡(jiǎn)強(qiáng);廖文俊;遲素敏;李承新;;Rab23在鱗癌細(xì)胞系中的表達(dá)及其對(duì)鱗癌細(xì)胞侵襲的影響[J];現(xiàn)代生物醫(yī)學(xué)進(jìn)展;2012年13期

5 郝建，叢勤滋，賈成芝，謝行恕，，張勇，汪桂華;食管鱗癌細(xì)胞軟X線顯微成象[J];中華物理醫(yī)學(xué)雜志;1994年03期

6 孫迎春;低劑量γ射線預(yù)照射人鱗癌細(xì)胞導(dǎo)致對(duì)低劑量順鉑處理的抗性增強(qiáng)[J];國(guó)外醫(yī)學(xué)(放射醫(yī)學(xué)核醫(yī)學(xué)分冊(cè));2000年01期

7 楊云生，李繼昌，徐峰;食管鱗癌細(xì)胞石蠟切片轉(zhuǎn)鐵球蛋白受體的檢測(cè)[J];河南醫(yī)科大學(xué)學(xué)報(bào);1994年03期

8 溫祥云;圖像分析儀對(duì)鱗癌細(xì)胞核的定量測(cè)定[J];首都醫(yī)科大學(xué)學(xué)報(bào);1997年01期

9 孫秀靜;原標(biāo);朱圣韜;李鵬;徐有青;;沉默PHF8重組慢病毒的制備及其對(duì)食管鱗癌細(xì)胞增生的影響[J];首都醫(yī)科大學(xué)學(xué)報(bào);2014年01期

10 楊麗娟;張莉;;BMI-1在不同時(shí)期表皮鱗癌細(xì)胞中的表達(dá)[J];社區(qū)醫(yī)學(xué)雜志;2009年11期

相關(guān)會(huì)議論文 前10條

1 劉丹;閔瑋;駱丹;顧寧;;膠體金對(duì)表皮鱗癌細(xì)胞影響的初步研究[A];2010全國(guó)中西醫(yī)結(jié)合皮膚性病學(xué)術(shù)會(huì)議論文匯編[C];2010年

2 宗曄;張澍田;;尼古丁對(duì)食管鱗癌細(xì)胞侵襲能力的影響及環(huán)氧化酶-2抑制劑對(duì)該作用的影響[A];中華醫(yī)學(xué)會(huì)第七次全國(guó)消化病學(xué)術(shù)會(huì)議論文匯編（下冊(cè)）[C];2007年

3 楊宏宇;鄒多宏;儲(chǔ)眉;郝艷紅;張芳婷;;轉(zhuǎn)人B7-H3基因鱗癌細(xì)胞系的建立及瘤苗的制備[A];第五次全國(guó)口腔頜面—頭頸腫瘤學(xué)術(shù)研討會(huì)論文匯編[C];2006年

4 付萌;張衍國(guó);劉玉峰;陳妍;王秋楓;李巍;;抗角蛋白自身抗體對(duì)體外培養(yǎng)鱗癌細(xì)胞端粒酶活性的影響[A];2002中國(guó)中西醫(yī)結(jié)合皮膚性病學(xué)術(shù)會(huì)議論文匯編[C];2002年

5 肖斌;施瑞華;朱宏;杜琰萍;張捷;;缺氧誘導(dǎo)因子-1α基因沉默食管鱗癌細(xì)胞株的構(gòu)建及HIF-1α基因在食管鱗癌細(xì)胞中功能的初步研究[A];中華醫(yī)學(xué)會(huì)第七次全國(guó)消化病學(xué)術(shù)會(huì)議論文匯編（下冊(cè)）[C];2007年

6 田芳;江亞南;張曉艷;趙繼敏;陳平;;姜黃素下調(diào)IκBα磷酸化對(duì)食管鱗癌細(xì)胞周期的影響[A];中國(guó)病理生理學(xué)會(huì)第九屆全國(guó)代表大會(huì)及學(xué)術(shù)會(huì)議論文摘要[C];2010年

7 王升志;高向東;孫玲;成洲;畢洪廣;毛祖彝;王大章;;熱化療對(duì)頜面部鱗癌細(xì)胞HSP70表達(dá)的影響[A];第五次全國(guó)口腔頜面—頭頸腫瘤學(xué)術(shù)研討會(huì)論文匯編[C];2006年

8 施瑞華;張捷;肖斌;張國(guó)新;郝波;;RNA干擾對(duì)食管鱗癌細(xì)胞缺氧誘導(dǎo)因子-1α抑制效果的體內(nèi)研究[A];中華醫(yī)學(xué)會(huì)第七次全國(guó)消化病學(xué)術(shù)會(huì)議論文匯編（下冊(cè)）[C];2007年

9 肖斌;施瑞華;杜琰萍;朱宏;林艷;;食管鱗癌細(xì)胞中缺氧誘導(dǎo)因子-1α與基質(zhì)金屬蛋白酶-2相關(guān)性研究[A];中華醫(yī)學(xué)會(huì)第七次全國(guó)消化病學(xué)術(shù)會(huì)議論文匯編（下冊(cè)）[C];2007年

10 肖斌;施瑞華;杜琰萍;朱宏;凌亭生;林艷;;載體介導(dǎo)shRNA特異性抑制食管鱗癌細(xì)胞Eca-109綠色熒光蛋白基因的表達(dá)[A];中華醫(yī)學(xué)會(huì)第七次全國(guó)消化病學(xué)術(shù)會(huì)議論文匯編（下冊(cè)）[C];2007年

相關(guān)博士學(xué)位論文 前10條

1 張坤;E2F1調(diào)控microRNAs對(duì)食管鱗癌細(xì)胞生物學(xué)功能的影響及機(jī)制研究[D];第三軍醫(yī)大學(xué);2015年

2 張松;Caveolin-1在食管鱗癌中的表達(dá)及其調(diào)控食管鱗癌細(xì)胞多藥耐藥性的機(jī)制研究[D];鄭州大學(xué);2016年

3 仲晨曦;HMGCR對(duì)食管鱗癌細(xì)胞惡性行為的影響及分子機(jī)制研究[D];上海交通大學(xué);2015年

4 李洪艷;甲基化對(duì)鱗癌細(xì)胞中巖藻糖基轉(zhuǎn)移酶IV基因表達(dá)的調(diào)控及對(duì)細(xì)胞增殖影響的研究[D];大連醫(yī)科大學(xué);2012年

5 李娟;NF-κB調(diào)控microRNAs對(duì)食管鱗癌細(xì)胞的生物學(xué)作用及機(jī)制研究[D];第三軍醫(yī)大學(xué);2012年

6 張薇;硒作用于食管鱗癌細(xì)胞的調(diào)控機(jī)制研究[D];中國(guó)協(xié)和醫(yī)科大學(xué);2010年

7 馬俊芬;調(diào)控食管鱗癌細(xì)胞CAR的表達(dá)對(duì)溶瘤腺病毒H101抗癌作用影響[D];鄭州大學(xué);2010年

8 汪斌;食管鱗癌組織與轉(zhuǎn)移淋巴結(jié)中的鱗癌細(xì)胞的蛋白質(zhì)組學(xué)研究[D];重慶醫(yī)科大學(xué);2007年

9 胡琛霏;甲基硒酸調(diào)控食管鱗癌細(xì)胞表觀遺傳改變的機(jī)制研究[D];北京協(xié)和醫(yī)學(xué)院;2014年

10 匡葉紅;CD147在人上皮鱗癌細(xì)胞多藥耐藥中的作用及機(jī)制研究[D];中南大學(xué);2009年

相關(guān)碩士學(xué)位論文 前10條

1 陳亮;MiRNA-1對(duì)食管鱗癌細(xì)胞KYSE510增殖、侵襲的影響及相關(guān)機(jī)制的研究[D];河北醫(yī)科大學(xué);2015年

2 楊露;Ets2對(duì)食管鱗癌細(xì)胞生長(zhǎng)、侵襲及mTOR/p70S6K分子信號(hào)的調(diào)控作用[D];鄭州大學(xué);2015年

3 劉靈;缺氧在食管鱗癌細(xì)胞上皮-間質(zhì)轉(zhuǎn)化及干細(xì)胞化中的作用[D];鄭州大學(xué);2015年

4 王欣桐;新型HSP90抑制劑BIIB021增強(qiáng)食管鱗癌細(xì)胞放射敏感性的研究[D];山東大學(xué);2015年

5 王爍;miR-503靶基因PRKACA的鑒定及其在食管鱗癌細(xì)胞中的生物學(xué)功能[D];四川醫(yī)科大學(xué);2015年

6 鄒多宏;鱗癌細(xì)胞的hB7-H3基因轉(zhuǎn)染及其檢測(cè)[D];安徽醫(yī)科大學(xué);2007年

7 付萌;抗角蛋白自身抗體對(duì)鱗癌細(xì)胞端粒酶活性的影響[D];第四軍醫(yī)大學(xué);2002年

8 馮亞?wèn)|;YC－1對(duì)食管鱗癌細(xì)胞Eca109缺氧誘導(dǎo)因子-1α表達(dá)的抑制作用[D];南京醫(yī)科大學(xué);2009年

9 毛麗紅;杜氏鹽藻FLA8在鞭毛中的定位及其對(duì)食管鱗癌細(xì)胞的作用[D];鄭州大學(xué);2013年

10 儲(chǔ)眉;轉(zhuǎn)人B7-H3基因鱗癌細(xì)胞瘤苗誘導(dǎo)抗腫瘤免疫應(yīng)答的體外研究[D];安徽醫(yī)科大學(xué);2008年

本文編號(hào)：2210044