Chen Jing-Jing, Hong Ge, Gao Li-Jing, Liu Tian-Jun, Cao Wen-Jun
Central Laboratory of Heping Hospital, Changzhi Medical College, Changzhi City, 046000, Shanxi Province, People's Republic of China.
J Cancer Res Clin Oncol. 2015 Sep;141(9):1553-61. doi: 10.1007/s00432-015-1918-1. Epub 2015 Jan 22.
Photodynamic therapy (PDT) is a promising treatment in cancer therapy, based on the use of a photosensitizer activated by visible light in the presence of oxygen. Nowadays significant research efforts have been focused on finding a new photosensitizer. In the present paper, the antitumor effects of a novel porphyrin-based photosensitizer, {Carboxymethyl-[2-(carboxymethyl-{[4-(10,15,20-triphenylporphyrin-5-yl)-phenylcarbamoyl]-methyl}-amino)-ethyl]-amino}-acetic acid (ATPP-EDTA) on two types of human malignant tumor cells in vitro and a gastric cancer model in nude mice, were evaluated.
The PDT efficacy with ATPP-EDTA in vitro was assessed by MTT assay. The intracellular accumulation was detected with fluorescence spectrometer, and the intracellular distribution was determined by laser scanning confocal microscopy. The mode of cell death was investigated by Hoechst 33342 staining and flow cytometer. BGC823-derived xenograft tumor model was established to explore the in vivo antitumor effects of ATPP-EDTA.
ATPP-EDTA exhibited intense phototoxicity on both cell lines in vitro in concentration- and light dose-dependent manners meanwhile imposing minimal dark cytotoxicity. The accumulation of ATPP-EDTA in two malignant cell lines was time-dependent and prior compared to normal cells. It was mainly localized at lysosomes, but induced cell death by apoptotic pathway. ATPP-EDTA significantly inhibited the growth of BGC823 tumors in nude mice (160 mW/cm(2), 100 J/cm(2)).
Present studies suggest that ATPP-EDTA is an effective photosensitizer for PDT to tumors. It distributed in lysosomes and caused cell apoptosis. ATPP-EDTA, as a novel photosensitizer, has a great potential for human gastric cancer treatment in PDT and deserves further investigations.
光动力疗法（PDT）是一种很有前景的癌症治疗方法，其基于在氧气存在下利用可见光激活的光敏剂。如今，大量研究工作都集中在寻找新型光敏剂上。在本文中，评估了一种新型卟啉基光敏剂{羧甲基-[2-(羧甲基-{[4-(10,15,20-三苯基卟啉-5-基)-苯基氨基甲酰基]-甲基}-氨基)-乙基]-氨基}-乙酸（ATPP-EDTA）对两种人恶性肿瘤细胞系的体外抗肿瘤作用以及对裸鼠胃癌模型的作用。
通过MTT法评估ATPP-EDTA在体外的光动力疗法疗效。用荧光光谱仪检测细胞内积累情况，并用激光扫描共聚焦显微镜确定细胞内分布。通过Hoechst 33342染色和流式细胞仪研究细胞死亡方式。建立BGC823衍生的异种移植肿瘤模型以探索ATPP-EDTA的体内抗肿瘤作用。
ATPP-EDTA在体外对两种细胞系均表现出强烈的光毒性，呈浓度和光剂量依赖性，同时暗细胞毒性极小。ATPP-EDTA在两种恶性细胞系中的积累具有时间依赖性，且比正常细胞更早。它主要定位于溶酶体，但通过凋亡途径诱导细胞死亡。ATPP-EDTA显著抑制裸鼠体内BGC823肿瘤的生长（160 mW/cm²，100 J/cm²）。
目前的研究表明，ATPP-EDTA是一种有效的肿瘤光动力疗法光敏剂。它分布于溶酶体并导致细胞凋亡。ATPP-EDTA作为一种新型光敏剂，在光动力疗法治疗人类胃癌方面具有巨大潜力，值得进一步研究。
