新型光敏剂2-丁胺-2-去甲氧基竹红菌乙素光动力作用诱导Capan-1细胞凋亡的实验研究

Apoptosis of human pancreatic cancer cell line Capan-1 induced by a novel photosensitizer 2-bytylamino-2 demethoxy hypocrellin B

目的 以新型光敏剂 2 丁胺 2 去甲氧基竹红菌乙素 (2 BA 2 DMHB)为研究对象 ,研究其光动力作用诱导人胰腺癌细胞 (Capan 1)凋亡。 方法 利用荧光分光光度计、MTT、细胞凋亡DNA梯带、流式细胞仪等技术研究 2 BA 2 DMHB对人胰腺癌细胞的杀伤作用、诱导细胞凋亡的特征。结果 2 BA 2 DMHB在 10～ 15min内被Capan 1细胞摄取 ,以后基本保持动态平衡。低浓度时主要定位于线粒体 ,高浓度时也定位于溶酶体。 0 5 μM ,4J/cm2 红光照射下细胞抑制率达 5 0 %以上 ,8μM ,4J/cm2 红光照射下细胞抑制率接近 90 %。在 4J/cm2 红光照射下光增强因子在 2 0 0以上。DNA琼脂糖电泳分析显示特征性细胞凋亡DNA梯带 ,流式细胞仪检测有明显凋亡发生 ,透射电镜分析显示特征性的凋亡小体和核着边现象。结论 2 BA 2 DMHB在低浓度时光动力作用具有较高细胞抑制作用 ,其光动力作用机制与细胞凋亡有关 ,是一种有重要应用前景的光敏剂。

Objective To investigate the inductive effects of a novel photosensitizer 2 bytylamino 2 demethoxy hypocrellin B (2 BA 2DMHB) on apoptosis of human pancreatic cancer cell line Capan 1. Methods The uptake and localization of 2 BA 2DMHB in Capan 1 cells and its inductive effects on apoptosis of the cells were determined with fluorospectrophotometry, MTT, DNA gel electrophoresis and flow cytometry. Results The rapid uptake of 2 BA 2DMHB was found in the first 10 15 min of incubation. No further photosensitizer was absorbed during the future time. The low concentration photosensitizer was mainly localized in mitochondria and also in lysosomes when the concentration was high. 2 BA 2DMHB exhibited stronger phototoxicity and much higher photopotentiation factor. An examination of morphology, DNA ladder analysis and FCM showed its activity of inducing cell apoptosis. Conclusions 2 BA 2DMHB is a potential photosensitizer and its phototoxicity to Capan 1 cells can result in apoptosis.