He Peijie, Bo Shen, Chung Phil-Sang, Ahn Jin-Chul, Zhou Liang
Department of Otolaryngology-Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai 200031, P.R. China; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, P.R. China.
Institute of Radiation Medicine, Fudan University, Shanghai 200032, P.R. China.
Oncol Lett. 2016 Sep;12(3):1889-1895. doi: 10.3892/ol.2016.4889. Epub 2016 Jul 20.
The present study aimed to investigate the effect, and elucidate the potential mechanisms, of 9-hydroxypheophorbide α-based photodynamic therapy (9-HPbD-PDT) on apoptosis and necrosis induction, and migration suppression of laryngeal cancer AMC-HN-3 (HN-3) cells. Phototoxicity initiated by 9-HPbD-PDT on HN-3 cells was observed in a photosensitizer dose-dependent pattern. There was an initial increase of apoptotic cells coupled with gradual enhancement of reactive oxygen series (ROS) generation at lower doses of 9-HPbD. By contrast, at a higher dose of 9-HPbD, there was a clear increase of necrotic cells with a gradual decrease of ROS generation. Following PDT, an elevated percentage of apoptotic cells with shrinkage or condensing nuclei was observed using Hoechst 33342/propidium iodide double staining, and an upregulated expression of poly ADP-ribose polymerase was detected through western blotting. A disruption of the mitochondrial membrane potential was detected 2 h following PDT. Significant suppression of cell migration and downregulation of epidermal growth factor receptor (EGFR) expression were recorded following PDT. These results indicate that the distribution of photosensitizer leads to differences in the generation of ROS, which subsequently determines the type of cell death. Overall, mitochondrial activation under oxidative stress is important in the 9-HPbD-PDT-induced apoptosis of HN-3 cells. Migration suppression of HN-3 cells following PDT may be associated with the inhibited expression of EGFR, due to oxidative stress.
本研究旨在探讨基于9-羟基脱镁叶绿酸α的光动力疗法(9-HPbD-PDT)对喉癌AMC-HN-3(HN-3)细胞凋亡、坏死诱导及迁移抑制的作用,并阐明其潜在机制。观察到9-HPbD-PDT对HN-3细胞引发的光毒性呈光敏剂剂量依赖性。在较低剂量的9-HPbD作用下,凋亡细胞最初增加,同时活性氧系列(ROS)生成逐渐增强。相比之下,在较高剂量的9-HPbD作用下,坏死细胞明显增加,而ROS生成逐渐减少。光动力疗法后,使用Hoechst 33342/碘化丙啶双重染色观察到凋亡细胞百分比升高,细胞核出现收缩或凝聚,通过蛋白质免疫印迹法检测到聚ADP-核糖聚合酶表达上调。光动力疗法后2小时检测到线粒体膜电位破坏。光动力疗法后记录到细胞迁移受到显著抑制,表皮生长因子受体(EGFR)表达下调。这些结果表明,光敏剂的分布导致ROS生成的差异,进而决定细胞死亡类型。总体而言,氧化应激下的线粒体激活在9-HPbD-PDT诱导的HN-3细胞凋亡中起重要作用。光动力疗法后HN-3细胞迁移抑制可能与氧化应激导致的EGFR表达受抑制有关。