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Down‐regulation of heat‐shock protein 27–induced resistance to photodynamic therapy in oral cancer cells
Authors:Jisun Kim  Hyuncheol Jung  Wonbong Lim  Sangwoo Kim  Youngjong Ko  Sandeep Karna  Oksu Kim  Yooduk Choi  Hongran Choi  Okjoon Kim
Institution:1. 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;2. Department of Periodontics, Dental Science Research Institute, Chonnam National University, Bug‐Gu, Gwangju, Korea;3. Department of Pathology, Faculty of Medicine, Chonnam National University, Bug‐Gu, Gwangju, Korea
Abstract: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/cm2. 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.
Keywords:Photodynamic therapy (PDT)  cell death  heat‐shock protein 27 (HSP27)
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