Apogossypolone誘導PC12細胞凋亡及逆轉(zhuǎn)EMT的作用機制研究
發(fā)布時間：2022-01-12 00:28
目的:嗜鉻細胞瘤（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,與PHEO惡性生物學行為密切相關(guān)。因此,本研究通過體內(nèi)外實驗試圖明確靶向bcl-2蛋白的小分子抑制劑ApoG2在PHEO中的治療價值,并探究其作用機制。方法:應(yīng)用CCK8實驗、劃痕實驗和Transwell實驗分別檢測AopG2對嗜鉻細胞瘤細胞系PC12細胞的增殖、遷移和侵襲功能的影響,流式細胞技術(shù)明確是否發(fā)生細胞凋亡和細胞周期阻滯,細胞免疫熒光實驗觀測細胞內(nèi)蛋白分子的表達分布及水平,然后用Western blot實驗深入探討ApoG2引發(fā)細胞功能改變的分子機制,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ApoG2通過誘導PC12細胞凋亡發(fā)揮抗腫瘤效果,延緩移植瘤生長;其分子機制可能是ApoG2拮抗抗凋亡蛋白bcl-2而間接釋放促凋亡蛋白bax,進而...
【文章來源】：上海交通大學上海市 211工程院校 985工程院校 教育部直屬院校
【文章頁數(shù)】：74 頁
【學位級別】：碩士
【部分圖文】：
AopG2呈時間、濃度依賴性抑制PC12細胞活性
圖 2. ApoG2 誘導細胞凋亡。A. 已觀察到細胞呈凋亡形態(tài)學改變，如細胞皺縮、變圓，突觸消失等；B. Hoechst 染色結(jié)果提示細胞核呈高亮狀態(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.
上海交通大學醫(yī)學院碩士學位論文圖 3. ApoG2 呈時間、濃度依賴性誘導 PC12 細胞發(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】：
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
【文章來源】：上海交通大學上海市 211工程院校 985工程院校 教育部直屬院校
【文章頁數(shù)】：74 頁
【學位級別】：碩士
【部分圖文】：
AopG2呈時間、濃度依賴性抑制PC12細胞活性
圖 2. ApoG2 誘導細胞凋亡。A. 已觀察到細胞呈凋亡形態(tài)學改變，如細胞皺縮、變圓，突觸消失等；B. Hoechst 染色結(jié)果提示細胞核呈高亮狀態(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.
上海交通大學醫(yī)學院碩士學位論文圖 3. ApoG2 呈時間、濃度依賴性誘導 PC12 細胞發(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】：
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
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