Department of Oral Pathology, 2nd stage of Brain Korea 21 for School of Dentistry, Dental Science Research Institute, Chonnam National University, Bug-Gu, Gwangju, Korea.
J Oral Pathol Med. 2013 Jan;42(1):9-16. doi: 10.1111/j.1600-0714.2012.01155.x. Epub 2012 May 5.
Photodynamic therapy (PDT) of cells is a new treatment modality involving selective delivery of a photosensitive dye into target cells, followed by visible light irradiation. PDT induces cell death by excessive ROS generation. The effects of multiple photosensitizers were owing to the difference in cell types involving sensitizer-specific protein changes linked to resistance. HSP27 is regulated in response to stress and is associated with apoptotic process. The effects of HSP27 on PDT resistance are controversial and unclear. The purpose of this study was to investigate the role of HSP27 down-regulation in the PDT-induced cells and HSP27 regulation in the resistance to PDT. KB cells transfected with HSP27 siRNA were exposed to hematoporphyrin (HP) followed by irradiation at 635 nm at an energy density of 4.5 mW/cm(2). After irradiation, the effects on HSP27 down-regulation were assessed by MTT assay, flow cytometry, confocal analysis, Western blotting and caspase activity. The results of this study showed that down-regulation of HSP27 restored cell survival in HP-PDT-induced apoptotic KB cells. HSP27 down-regulation attenuated PDT-induced apoptosis through caspase-mediated pathway in KB cells. Also, HSP27 silencing regulated Bax, Bcl-2, and PARP protein expression in PDT-induced cells. Therefore, HSP27 down-regulation confers resistance to PDT through interruption of apoptotic protein activity in PDT-induced cell death. HSP27 might contribute to regulating PDT-induced apoptosis in PDT-resistant cells.
光动力疗法（PDT）是一种新的治疗方法，涉及将光敏染料选择性地递送到靶细胞中，然后进行可见光照射。PDT 通过过度产生 ROS 诱导细胞死亡。多种光敏剂的作用是由于涉及与抗性相关的敏化剂特异性蛋白变化的细胞类型的差异。HSP27 响应应激而被调节，并与凋亡过程相关。HSP27 对 PDT 抗性的影响存在争议且不清楚。本研究的目的是研究 HSP27 下调在 PDT 诱导的细胞中的作用以及 HSP27 对 PDT 抗性的调节作用。用 HSP27 siRNA 转染的 KB 细胞用血卟啉（HP）孵育，然后在 635nm 波长下以 4.5mW/cm2 的能量密度进行照射。照射后，通过 MTT 测定、流式细胞术、共聚焦分析、Western blot 和 caspase 活性评估 HSP27 下调的影响。本研究结果表明，HSP27 的下调恢复了 HP-PDT 诱导的凋亡 KB 细胞中的细胞存活。HSP27 下调通过 caspase 介导的途径减弱了 KB 细胞中 PDT 诱导的细胞凋亡。此外，HSP27 沉默调节了 PDT 诱导的细胞中 Bax、Bcl-2 和 PARP 蛋白的表达。因此，HSP27 的下调通过中断凋亡蛋白在 PDT 诱导的细胞死亡中的活性赋予了对 PDT 的抗性。HSP27 可能有助于调节 PDT 耐药细胞中的 PDT 诱导的细胞凋亡。
