HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death.
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.
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
He-Xiao
HX
Wang
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Yang
Y
Yang
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Hao
H
Guo
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Dian-Dong
DD
Hou
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Song
S
Zheng
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Yu-Xiao
YX
Hong
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Yun-Fei
YF
Cai
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Wei
W
Huo
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Rui-Qun
RQ
Qi
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Li
L
Zhang
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Hong-Duo
HD
Chen
Department of Dermatology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
Xing-Hua
XH
Gao
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D055785:Gene Knockdown Techniques; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins
HSPB1; combination strategy; hyperthermia; melanoma; thermotolerance