药学学报, 2019, 54(12): 2251-2255
引用本文:
谷长维, 张玲, 谷鸣. 新型光敏剂BF01光动力治疗人肝癌机制初步研究[J]. 药学学报, 2019, 54(12): 2251-2255.
GU Chang-wei, ZHANG Ling, GU Ming. Experimental study of photodynamic therapy using a new photosensitizer BF01 for human liver cancer[J]. Acta Pharmaceutica Sinica, 2019, 54(12): 2251-2255.

新型光敏剂BF01光动力治疗人肝癌机制初步研究
谷长维, 张玲, 谷鸣
上海百菲生物医药科技有限公司, 上海 201203
摘要:
本文探讨光敏剂二氢卟吩e6钛合物BF01光动力对人肝癌细胞株BEL-7402体外杀伤效应和体内抑瘤效应及其作用机制。实验采用CCK-8法检测同一激光强度不同给药浓度(0、0.8、1.6、3.2、6.4 μmol·L-1)的光敏剂BF01光动力对BEL-7402细胞的抑制率和半数抑制浓度(IC50),通过流式细胞术检测BEL-7402细胞死亡方式,DAPI染色观察细胞凋亡特征,光动力照射后检测BEL-7402活性氧、共聚焦显微镜观察亚细胞定位,建立裸鼠人肝癌细胞模型,绘制肿瘤生长曲线,观察治疗效果,动物实验经华东理工大学伦理委员会批准。实验结果显示,BF01-PDT治疗组能明显抑制BEL-7402肿瘤细胞增殖,BF01的浓度为6.4 μmol·L-1时,其杀伤率达86%,IC50是2.46 μmol·L-1,检测细胞死亡方式主要是以晚期凋亡为主,DAPI染色细胞核的形态呈现出凋亡的特征,活性氧水平随给药浓度增加而增加,亚细胞定位在线粒体。体内实验表明,光敏剂BF01介导的光动力疗法对人肝癌细胞及小鼠体内肿瘤生长抑制作用明显,因此新型BF01光敏剂具备良好的应用前景。
关键词:    肝癌      光敏剂      凋亡      亚细胞定位      裸鼠模型     
Experimental study of photodynamic therapy using a new photosensitizer BF01 for human liver cancer
GU Chang-wei, ZHANG Ling, GU Ming
Shanghai Baifei Biomedical Technology Co., Ltd., Shanghai 201203, China
Abstract:
We study here in vitro cytotoxicity, in vivo tumor inhibition and the mechanism on photodynamic therapy (PDT) of photosensitizer BF01 using human hepatocellular carcinoma cell line BEL-7402. CCK-8 method was used to detect the inhibition rate and IC50 in BEL-7402 cells on the same laser intensity with varying concentrations (0, 0.8, 1.6, 3.2, 6.4 μmol·L-1) of photosensitizer BF01. Cell death mode of BEL-7402 was detected by flow cytometry, with apoptotic characteristics observed by DAPI staining, and the subcellular localization of reactive oxygen was observed using photodynamic detection and confocal microscopy. The cell model of human liver cancer in nude mice was established, tumor growth curve was drawn, and the therapeutic effect of BF01 was determined. The animal experimentation was approved by East China University of Science and Technology Ethics Committee. The results indicated that BF01 PDT treatment can clearly inhibit BEL-7402 tumor cell proliferation, with the killing rate of 86% at the concentration of 6.4 μmol·L-1 of BF01, and half lethal concentration IC50 value of 2.46 μmol·L-1. DAPI stained nuclei shows the characteristics of advanced stage apoptosis, whereas reactive oxygen species level in the mitochondria increased with increasing drug concentration. In vivo experiments showed that photosensitizer BF01 mediated photodynamic therapy of liver cancer cells and inhibited tumor growth in mice. Therefore, the new BF01 photosensitizer has a potential for development into future clinic application.
Key words:    liver cancer    photosensitizer    apoptosis    subcellular localization    nude mouse model   
收稿日期: 2019-01-09
DOI: 10.16438/j.0513-4870.2019-0220
基金项目: 上海市科技创新行动计划(17431904600).
通讯作者: 谷长维,Tel:86-21-58602838,E-mail:gcw106@163.com
Email: gcw106@163.com
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