HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death
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He-Xiao Wang1, Yang Yang1, Hao Guo1, Dian-Dong Hou1, Song Zheng1, Yu-Xiao Hong1, Yun-Fei Cai1, Wei Huo1, Rui-Qun Qi1, Li Zhang1, Hong-Duo Chen1, Xing-Hua Gao1
1Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China
Xing-Hua Gao, email: [email protected]
Keywords: hyperthermia, thermotolerance, HSPB1, combination strategy, melanoma
Received: December 14, 2015 Accepted: August 22, 2016 Published: September 08, 2016
Hyperthermia has shown clinical potency as a single agent or as adjuvant to other therapies in cancer treatment. However, thermotolerance induced by thermosensitive genes such as the heat shock proteins can limit the efficacy of hyperthermic treatment. In the present study, we identified HSPB1 (HSP27) is hyperthermically inducible or endogenously highly expressed in both murine and human melanoma cell lines. We used a siRNA strategy to reduce HSPB1 levels and showed increased intolerance to hyperthermia via reduced cell viability and/or proliferation of cells. In the investigation of underlying mechanisms, we found knock down of HSPB1 further increased the proportion of apoptotic cells in hyperthermic treated melanoma cells when compared with either single agent alone, and both agents leaded to cell cycle arrest at G0/G1 or G2/M phases. We concluded that hyperthermia combined with silencing of HSPB1 enhanced cell death and resulted in failure to thrive in melanoma cell lines, implying the potential clinical utility of hyperthermia in combination with HSPB1 inhibition in cancer treatment.
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