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新型光敏剂DTPP与650纳米激光联合使用可导致肺癌A549细胞发生有效凋亡、细胞周期停滞及细胞骨架蛋白变化。

Combination of a novel photosensitizer DTPP with 650 nm laser results in efficient apoptosis, arresting cell cycle and cytoskeleton protein changes in lung cancer A549 cells.

作者信息

Wang H, Zhang H M, Yin H J, Wei M Q, Sha H, Liu T J, Li Y X

机构信息

Laboratory of Laser Medicine, Institute of Biomedical Engineering, Academy of Medical Science and Peking Union Medical College, Tianjin, 300192, China,

出版信息

Lasers Med Sci. 2015 Jan;30(1):77-82. doi: 10.1007/s10103-014-1617-1. Epub 2014 Jun 26.

Abstract

Photodynamic therapy (PDT) using photosensitized reaction to produce cytotoxicity was used for cancer therapy in recent years. To study the effectiveness of PDT mediated by a novel photosensitizer (PS), DTPP 5-(4'-(2″-dicarboxymethylamino)acetamidophenyl)-10, 15, 20-triphenylporphyrin, on lung cancer A549 cell lines in vitro, DTPP was employed in different concentrations (2, 4, 6, 8, 10, 12, 15, 20, 25, and 30 μg/ml) and combined with 650 nm laser of different power densities (0.6, 1.2, 2.4, 4.8, 7.2, and 9.6 J/cm(2)) that resulted in obvious inhibition of cell proliferation and apoptosis. Results showed that cell survival rates have a dependent relationship with time and PS concentrations and no significant cytotoxicity was induced by DTPP itself. Apoptosis and cell cycle S arrest were observed; cytoskeleton morphologic observation revealed collapse, sparkling, and shrunken shapes. Apoptosis-related protein caspase-3 overexpression was detected while caspase-9, bcl-2, and cytoskeleton protein beta-catenin were in low levels of expression than the control. Cleavage of beta-catenin by caspase-3 or other proteases from the lysosome might be the main reason for the cytoskeleton collapse as beta-tubulin and actin were at a stable level 12 h after PDT. This paper gives a better understanding of the effectiveness of DTPP-mediated PDT in lung cancer A549 cells both with regard to dosimetry and apoptosis changes.

摘要

近年来,利用光敏反应产生细胞毒性的光动力疗法(PDT)被用于癌症治疗。为了研究新型光敏剂(PS)5-(4'-(2″-二羧甲基氨基)乙酰氨基苯基)-10, 15, 20-三苯基卟啉(DTPP)介导的光动力疗法对肺癌A549细胞系的体外有效性,采用不同浓度(2、4、6、8、10、12、15、20、25和30μg/ml)的DTPP,并结合不同功率密度(0.6、1.2、2.4、4.8、7.2和9.6 J/cm²)的650nm激光,结果导致细胞增殖和凋亡受到明显抑制。结果表明,细胞存活率与时间和PS浓度呈依赖关系,DTPP本身未诱导明显的细胞毒性。观察到凋亡和细胞周期S期阻滞;细胞骨架形态学观察显示塌陷、起泡和萎缩形状。检测到凋亡相关蛋白caspase-3过表达,而caspase-9、bcl-2和细胞骨架蛋白β-连环蛋白的表达水平低于对照组。PDT后12小时,β-微管蛋白和肌动蛋白处于稳定水平,caspase-3或溶酶体中的其他蛋白酶对β-连环蛋白的切割可能是细胞骨架塌陷的主要原因。本文从剂量学和凋亡变化方面更好地了解了DTPP介导的光动力疗法对肺癌A549细胞的有效性。

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