Apogossypolone诱导PC12细胞凋亡及逆转EMT的作用机制研究
发布时间：2022-01-12 00:28
目的:嗜铬细胞瘤（Pheochromocytoma,PHEO）仅在转移病灶出现后才能确诊为恶性嗜铬细胞瘤（Malignant pheochromocytoma,MP）。而彼时,患者几乎无法从传统治疗手段中获益,致使疾病预后极差。既往研究表明抗凋亡蛋白bcl-2在MP中显著高表达,与PHEO恶性生物学行为密切相关。因此,本研究通过体内外实验试图明确靶向bcl-2蛋白的小分子抑制剂ApoG2在PHEO中的治疗价值,并探究其作用机制。方法:应用CCK8实验、划痕实验和Transwell实验分别检测AopG2对嗜铬细胞瘤细胞系PC12细胞的增殖、迁移和侵袭功能的影响,流式细胞技术明确是否发生细胞凋亡和细胞周期阻滞,细胞免疫荧光实验观测细胞内蛋白分子的表达分布及水平,然后用Western blot实验深入探讨ApoG2引发细胞功能改变的分子机制,最后通过构建裸鼠皮下移植瘤及转移瘤模型评估ApoG2在动物水平的抗肿瘤效果。结果:第一部分研究中,我们证实ApoG2通过诱导PC12细胞凋亡发挥抗肿瘤效果,延缓移植瘤生长;其分子机制可能是ApoG2拮抗抗凋亡蛋白bcl-2而间接释放促凋亡蛋白bax,进而...
【文章来源】：上海交通大学上海市 211工程院校 985工程院校 教育部直属院校
【文章页数】：74 页
【学位级别】：硕士
【部分图文】：
AopG2呈时间、浓度依赖性抑制PC12细胞活性
图 2. ApoG2 诱导细胞凋亡。A. 已观察到细胞呈凋亡形态学改变，如细胞皱缩、变圆，突触消失等；B. Hoechst 染色结果提示细胞核呈高亮状态。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.
上海交通大学医学院硕士学位论文图 3. ApoG2 呈时间、浓度依赖性诱导 PC12 细胞发生早期凋亡。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.
【参考文献】：
期刊论文
[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.. 癌症. 2011(01)
本文编号：3583740
【文章来源】：上海交通大学上海市 211工程院校 985工程院校 教育部直属院校
【文章页数】：74 页
【学位级别】：硕士
【部分图文】：
AopG2呈时间、浓度依赖性抑制PC12细胞活性
图 2. ApoG2 诱导细胞凋亡。A. 已观察到细胞呈凋亡形态学改变，如细胞皱缩、变圆，突触消失等；B. Hoechst 染色结果提示细胞核呈高亮状态。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.
上海交通大学医学院硕士学位论文图 3. ApoG2 呈时间、浓度依赖性诱导 PC12 细胞发生早期凋亡。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.
【参考文献】：
期刊论文
[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.. 癌症. 2011(01)
本文编号：3583740
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