Lee Hye Myeong, Chung Chung-Wook, Kim Cy Hyun, Kim Do Hyung, Kwak Tae Won, Jeong Young-Il, Kang Dae Hwan
National Research and Development Center for Hepatobiliary Cancer, Research Institute for Convergence of Biomedical Science and Technology, Yangsan, Republic of Korea.
Department of Biological Sciences, Andong National University, Andong, Republic of Korea.
Drug Des Devel Ther. 2014 Sep 18;8:1451-62. doi: 10.2147/DDDT.S62265. eCollection 2014.
In this study, the effect of chlorin e6-based photodynamic therapy (Ce6-PDT) was investigated in human intrahepatic (HuCC-T1) and extrahepatic (SNU1196) cholangiocarcinoma (CCA) cells. The amount of intracellular Ce6 increased with increasing Ce6 concentration administered, or with incubation time, in both cell lines. The ability to take up Ce6 and generate reactive oxygen species after irradiation at 1.0 J/cm(2) did not significantly differ between the two CCA cell types. However, after irradiation, marked differences were observed for photodamage and apoptotic/necrotic signals. HuCC-T1 cells are more sensitive to Ce6-PDT than SNU1196 cells. Total glutathione (GSH) levels, glutathione peroxidase and glutathione reductase activities in SNU1196 cells were significantly higher than in HuCC-T1 cells. With inhibition of enzyme activity or addition of GSH, the phototoxic effect could be controlled in CCA cells. The intracellular level of GSH is the most important determining factor in the curative action of Ce6-PDT against tumor cells.
在本研究中，研究了基于二氢卟吩e6的光动力疗法（Ce6-PDT）对人肝内胆管癌（HuCC-T1）和肝外胆管癌（SNU1196）细胞的作用。在这两种细胞系中，细胞内Ce6的量随着给予的Ce6浓度增加或孵育时间延长而增加。在1.0 J/cm(2)照射后，两种胆管癌细胞类型摄取Ce6并产生活性氧的能力没有显著差异。然而，照射后，在光损伤和凋亡/坏死信号方面观察到明显差异。HuCC-T1细胞比SNU1196细胞对Ce6-PDT更敏感。SNU1196细胞中的总谷胱甘肽（GSH）水平、谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性显著高于HuCC-T1细胞。通过抑制酶活性或添加GSH，可以控制胆管癌细胞中的光毒性作用。细胞内GSH水平是Ce6-PDT对肿瘤细胞治疗作用中最重要的决定因素。
