FABP5在胶质瘤中的表达、功能及其与全反式维甲酸药物敏感性的关系
发布时间：2018-08-28 20:11
【摘要】：目的:不同胶质瘤细胞系对全反式维甲酸(ATRA)的反应不同,可能与脂肪酸结合5(FABP5)结合ATRA后激活促细胞增殖通路有关。此外,有研究报道,FABP5与肿瘤的发生、发展以及转移相关,而FABP5在胶质瘤中的功能尚不清楚。本研究旨在探讨FABP5蛋白在不同级别胶质瘤中的表达、功能及其与ATRA敏感性的关系,为后续进一步研究FABP5相关的胶质瘤靶向治疗药物提供新思路。方法:1.免疫组化检测23例肿瘤旁正常脑组织以及137例不同级别胶质瘤中FABP5的表达,统计分析FABP5的表达与临床病理参数之间的关系;并根据临床随访资料,绘制生存曲线。2.体外培养人脑胶质瘤细胞株A172、T98G和U251,利用蛋白免疫印迹法(Western blot)检测3种胶质瘤细胞系中FABP5蛋白表达水平;采用si RNA技术构建相关细胞模型,下调A172、T98G细胞中FABP5蛋白表达水平,利用噻唑蓝(MTT)比色法、划痕实验和Transwell法分别检测细胞增殖活力、迁移及侵袭变化。3.不同浓度ATRA(0,1,5,10mM)处理3种细胞,进行苏木素-伊红(HE)染色,观察用药前后胶质瘤细胞形态的变化;利用MTT法检测ATRA对胶质瘤细胞增殖活力的影响;利用Western blot和免疫细胞化学(ICC)法检测胶质瘤细胞用药前后FABP5蛋白表达变化。结果:1.FABP5在胶质瘤中的表达明显高于正常脑组织(P0.05),且与胶质瘤的组织学分级、预后相关(P均0.05)。2.FABP5在U251、A172、T98G细胞系中均有表达,表现出依次递增。与对照组相比较si RNA下调FABP5后能明显降低A172、T98G细胞的增殖活力,迁移和侵袭能力显著下调。3.用药前后三种细胞形态均无明显差异;MTT检测结果显示仅在48h时10mM ATRA对A172细胞有明显抑制细胞生长作用,不同浓度ATRA对A172、T98G细胞及1,5mM ATRA对A172均无明显抑制作用;用药前后FABP5蛋白总量及细胞亚分布均无明显改变。结论:FABP5可以促进胶质瘤细胞的增殖、迁移与侵袭能力,并与胶质瘤患者预后相关。胶质瘤细胞系对ATRA欠敏感,与FABP5蛋白的表达无明显相关性。
[Abstract]:AIM: Different glioma cell lines respond differently to all-trans retinoic acid (ATRA) and may be related to activation of the cell proliferation pathway after fatty acid binding 5 (FABP5) binding to ATRA. In addition, some studies have reported that FABP5 is associated with tumorigenesis, development and metastasis, while the function of FABP5 in glioma remains unclear. The expression and function of FABP5 in different grades of gliomas and the relationship between FABP5 and ATRA sensitivity provide new ideas for further study of FABP5-related targeted therapy drugs for gliomas. Methods: 1. Immunohistochemistry was used to detect the expression of FABP5 in 23 normal brain tissues adjacent to tumors and 137 gliomas of different grades. The expression of FABP5 protein in human glioma cell lines A172, T98G and U251 was detected by Western blot, and the related cell models were constructed by Si RNA technique to down-regulate the expression of FAB in A172 and T98G cells. P5 protein expression was detected by MTT colorimetry, scratch test and Transwell method respectively. 3. Three kinds of cells were treated with different concentrations of ATRA (0,1,5,10 mM) and stained with hematoxylin-eosin (HE) to observe the morphological changes of glioma cells before and after treatment. Results: 1. The expression of FABP5 in gliomas was significantly higher than that in normal brain tissues (P 0.05), and correlated with histological grade and prognosis of gliomas (P 0.05). 2. FABP5 was found in U251, A172, T98G cell lines. Compared with the control group, the proliferation activity, migration and invasion ability of A172 and T98G cells were significantly decreased after down-regulation of FABP5 by Si RNA. There was no significant inhibitory effect of ATRA on A172, T98G cells and 1,5mM ATRA, and no significant change in total FABP5 protein and cell subdistribution before and after treatment. Conclusion: FABP5 can promote the proliferation, migration and invasion of glioma cells, and is related to the prognosis of glioma patients. No significant correlation was found.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.41
[Abstract]:AIM: Different glioma cell lines respond differently to all-trans retinoic acid (ATRA) and may be related to activation of the cell proliferation pathway after fatty acid binding 5 (FABP5) binding to ATRA. In addition, some studies have reported that FABP5 is associated with tumorigenesis, development and metastasis, while the function of FABP5 in glioma remains unclear. The expression and function of FABP5 in different grades of gliomas and the relationship between FABP5 and ATRA sensitivity provide new ideas for further study of FABP5-related targeted therapy drugs for gliomas. Methods: 1. Immunohistochemistry was used to detect the expression of FABP5 in 23 normal brain tissues adjacent to tumors and 137 gliomas of different grades. The expression of FABP5 protein in human glioma cell lines A172, T98G and U251 was detected by Western blot, and the related cell models were constructed by Si RNA technique to down-regulate the expression of FAB in A172 and T98G cells. P5 protein expression was detected by MTT colorimetry, scratch test and Transwell method respectively. 3. Three kinds of cells were treated with different concentrations of ATRA (0,1,5,10 mM) and stained with hematoxylin-eosin (HE) to observe the morphological changes of glioma cells before and after treatment. Results: 1. The expression of FABP5 in gliomas was significantly higher than that in normal brain tissues (P 0.05), and correlated with histological grade and prognosis of gliomas (P 0.05). 2. FABP5 was found in U251, A172, T98G cell lines. Compared with the control group, the proliferation activity, migration and invasion ability of A172 and T98G cells were significantly decreased after down-regulation of FABP5 by Si RNA. There was no significant inhibitory effect of ATRA on A172, T98G cells and 1,5mM ATRA, and no significant change in total FABP5 protein and cell subdistribution before and after treatment. Conclusion: FABP5 can promote the proliferation, migration and invasion of glioma cells, and is related to the prognosis of glioma patients. No significant correlation was found.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.41
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