HSPB1 deficiency sensitizes melanoma cells to hyperthermia induced cell death
Autor: | Song Zheng, Yuxiao Hong, Hao Guo, Hong-Duo Chen, Xing-Hua Gao, Yun-Fei Cai, Dian-Dong Hou, Wei Huo, He-Xiao Wang, Yang Yang, Li Zhang, Ruiqun Qi |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Hyperthermia combination strategy Programmed cell death Cell cycle checkpoint animal structures Cell Survival HSP27 Heat-Shock Proteins Apoptosis thermotolerance 03 medical and health sciences Mice 0302 clinical medicine Hsp27 Cell Line Tumor medicine melanoma Animals Humans Viability assay Heat-Shock Proteins HSPB1 biology business.industry Melanoma Hyperthermia Induced medicine.disease hyperthermia Neoplasm Proteins 030104 developmental biology Oncology Cell culture 030220 oncology & carcinogenesis Gene Knockdown Techniques Immunology Cancer research biology.protein business Molecular Chaperones Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | 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. |
Databáze: | OpenAIRE |
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