多胺类似物BENS和TBP对胰腺癌PANC-1细胞增殖、凋亡和迁移能力的影响  

Effect of the Polyamine Analogues BENS and Tetrabutyl Propanediamine on Apoptosis and Migration of Human PANC1 Pancreatic Cancer Cells

作　　者：杨建林[1] 韩钰[1] 王凯[2] 张贺吉[1] 张军[1] 王艳林[1] 

机构地区：[1]三峡大学分子生物学研究所,中国湖北宜昌443002 [2]武汉工程大学湖北省新型反应器与绿色化学工艺重点实验室,中国湖北武汉430073

出　　处：《生命科学研究》2014年第2期145-150,共6页Life Science Research

基　　金：国家自然科学基金资助项目(30772590)

摘　　要：为探讨多胺类似物BENS和TBP对胰腺癌PANC-1细胞生长的影响、促进细胞凋亡的机制以及迁移能力的影响,运用MTT法检测药物对细胞生长的影响;亚凋亡峰流式细胞分析法及TUNEL法检测细胞凋亡;Western blotting法测定Bax蛋白、细胞色素C蛋白的表达变化;Ranswell技术检测细胞迁移能力的改变。分析发现,两种多胺类似物均可显著抑制PANC1癌细胞增殖,抑制作用随药物浓度加大而增加,其细胞毒性大小依次为BENS>TBP。细胞凋亡分析发现,BENS和TBP均可诱导PANC1发生细胞程序性凋亡,导致亚凋亡峰出现和明显的DNA断裂现象。胞浆中Bax蛋白和细胞色素C含量显著增加,同时显著性抑制PANC1细胞的迁移能力。表明BENS和TBP能够抑制人胰腺癌PANC1细胞增殖;阻止PANC1细胞迁移的能力;同时诱导细胞发生凋亡,其作用机制可能与改变肿瘤细胞正常的细胞周期,活化线粒体参与的细胞凋亡途径相关。In order to investigate the effects of the polyamine analogues BENS and tetrabutyl propanediamine （TBP） on the proliferation, apoptosis, and migration of human pancreatic cancer PANC1 cells and its poten- tial mechanism, methyl thiazolyl tetrazolium was used to analyze cell proliferation, and flow cytometry was performed to assay the cell cycles. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling as- say was used to identify the apoptotic cells. Western blot analysis was used to evaluate the expression of apoptosis-related proteins. The Transwell technique was used to analyze cell migration. TBP significantly in- hibited the proliferation and migration of PANC1 cells, and the inhibitory effect was time and dose depen- dent. The flow cytometry results indicated that TBP and BENS interfered with the cell cycles. Meanwhile, the number of apoptotic cells significantly increased. After BENS and TBP treatment, observation of the typ- ical behavior of apoptotic ceils revealed that the contents of the pro-apoptotic proteins Bax and cytochrome C significantly increased in the cytosol. The results showed that BENS and TBP can inhibit the proliferationand induce the apoptosis of human pancreatic cancer PANC 1 cells by interfering with the cell cycle and ac- tivating the mitochondrion-mediated apoptotic pathway.

关 键 词：多胺类似物 四丁基丙二胺(TBP) 双乙基异精胺(BENS) 胰腺癌细胞 细胞凋亡 

分 类 号：R979.1[医药卫生—药品]