Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells

Kim,Jisun; Lim,Haesoon; Kim,Sangwoo; Cho,Hyejung; Kim,Yong; Li,Xiaojie; Choi,Hongran; Kim,Okjoon

doi:10.3892/or.2016.4597

Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells

Authors:
- Jisun Kim
- Haesoon Lim
- Sangwoo Kim
- Hyejung Cho
- Yong Kim
- Xiaojie Li
- Hongran Choi
- Okjoon Kim
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Affiliations: Department of Oral Pathology, Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea, College of Stomatology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: January 26, 2016 https://doi.org/10.3892/or.2016.4597
Pages: 2237-2245

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Abstract

We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear. Therefore, in the present study, we investigated the effects of HSP27 and HSP70 on PDT-induced cell death of oral cancer cells through autophagy and apoptosis. Cancer cells were treated with hematoporphyrin at varying doses, followed by irradiation at 635 nm with an energy density of 5 mW/cm2. We determined the changes in HSP expression by determining the levels of PARP-1 and LC3II in PDT-resistant cells. Furthermore, we assessed cell death signaling after downregulating HSPs by transfecting specific siRNAs. We observed that PDT decreased HSP27 expression but increased HSP70 expression in the head and neck cancer cells. Treatment of cells with LC3II and PARP-1 inhibitors resulted in upregulation of HSP70 and HSP27 expression, respectively. Downregulation of HSP27 and HSP70 induced cell death and PDT resistance through autophagy and apoptosis. Moreover, downregulation of HSP27 in PDT-resistant cells resulted in enhanced survival. These results indicate that the regulation of HSP27 and HSP70 plays a principal role in increasing the effects of PDT by inducing autophagic and apoptotic cell death.

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