目的:嗜鉻細(xì)胞瘤（Pheochromocytoma,PHEO）僅在轉(zhuǎn)移病灶出現(xiàn)后才能確診為惡性嗜鉻細(xì)胞瘤（Malignant pheochromocytoma,MP）。而彼時,患者幾乎無法從傳統(tǒng)治療手段中獲益,致使疾病預(yù)后極差。既往研究表明抗凋亡蛋白bcl-2在MP中顯著高表達(dá),與PHEO惡性生物學(xué)行為密切相關(guān)。因此,本研究通過體內(nèi)外實(shí)驗(yàn)試圖明確靶向bcl-2蛋白的小分子抑制劑ApoG2在PHEO中的治療價值,并探究其作用機(jī)制。方法:應(yīng)用CCK8實(shí)驗(yàn)、劃痕實(shí)驗(yàn)和Transwell實(shí)驗(yàn)分別檢測AopG2對嗜鉻細(xì)胞瘤細(xì)胞系PC12細(xì)胞的增殖、遷移和侵襲功能的影響,流式細(xì)胞技術(shù)明確是否發(fā)生細(xì)胞凋亡和細(xì)胞周期阻滯,細(xì)胞免疫熒光實(shí)驗(yàn)觀測細(xì)胞內(nèi)蛋白分子的表達(dá)分布及水平,然后用Western blot實(shí)驗(yàn)深入探討ApoG2引發(fā)細(xì)胞功能改變的分子機(jī)制,最后通過構(gòu)建裸鼠皮下移植瘤及轉(zhuǎn)移瘤模型評估ApoG2在動物水平的抗腫瘤效果。結(jié)果:第一部分研究中,我們證實(shí)ApoG2通過誘導(dǎo)PC12細(xì)胞凋亡發(fā)揮抗腫瘤效果,延緩移植瘤生長;其分子機(jī)制可能是ApoG2拮抗抗凋亡蛋白bcl-2而間接釋放促凋亡蛋白bax,進(jìn)而... 

【文章來源】：上海交通大學(xué)上海市 211工程院校 985工程院校 教育部直屬院校

【文章頁數(shù)】：74 頁

【學(xué)位級別】：碩士

【部分圖文】：

AopG2呈時間、濃度依賴性抑制PC12細(xì)胞活性

圖 2. ApoG2 誘導(dǎo)細(xì)胞凋亡。A. 已觀察到細(xì)胞呈凋亡形態(tài)學(xué)改變，如細(xì)胞皺縮、變圓，突觸消失等；B. Hoechst 染色結(jié)果提示細(xì)胞核呈高亮狀態(tài)。Figure 2. ApoG2 could induce cell apoptosis. A. Morphological characteristics of apoptosis such asbecoming shrunken, rounded and decrease of synaptic structures were observed; B. Apoptosis cellnucleus presented bright blue in Hoechst 33258 assay.

上海交通大學(xué)醫(yī)學(xué)院碩士學(xué)位論文圖 3. ApoG2 呈時間、濃度依賴性誘導(dǎo) PC12 細(xì)胞發(fā)生早期凋亡。No statistical significance (ns),P>0.05; *, P<0.05; ***, P<0.001。Figure 3. ApoG2 could effectively induce PC12 cell early apoptosis by a dose- and time-dependentmanner. No statistical significance (ns), P>0.05; *, P<0.05; ***, P<0.001.

【參考文獻(xiàn)】：
期刊論文
[1]Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species[J]. Zhe-Yu Hu1,2,5, Jing Wang1,2, Gang Cheng3, Xiao-Feng Zhu1,2, Peng Huang3, Dajun Yang4, and Yi-Xin Zeng1,2State Key Laboratory of Oncology in South China, 1 Guangzhou, Guangdong 510060, P. R. China; 2Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China; 3Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; 4 Ascenta Therapeutics Incorporation, Malvern, Pennsylvania 19355, USA; The First Hospital 5 of Changsha City, Changsha, Hunan 410005, P. R. China..  癌癥. 2011(01)



本文編號：3583740