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01-07-2012 | Translational Research and Biomarkers

Inhibition of Heat Shock Protein Response Enhances PS-341-Mediated Glioma Cell Death

Authors: Yaohua Liu, MD, PhD, Tianhu Zheng, PhD, Shiguang Zhao, MD, PhD, Huailei Liu, MD, Dayong Han, MD, Yunbo Zhen, MD, PhD, Dongxiao Xu, MD, Yu Wang, MD, Hongyu Yang, MD, Guang Zhang, MD, Chunlei Wang, MD, Jianing Wu, MD, Yuanzhu Ye, MD

Published in: Annals of Surgical Oncology | Special Issue 3/2012

Abstract

Background

Previous study indicated that PS-341 induces cell death via JNK pathway in vitro in glioma. However, suppressing proteasome complex by PS-341 may induce expression of heat shock proteins (HSPs), which confer potential protection against cellular stress. In this study, we explored whether induction of HSPs could impair PS-341-induced cell death and whether inhibition of HSPs could enhance cell damage induced by PS-341 in glioma cells.

Methods

HSP expression in glioma cells was modulated by HSP inhibitor, sublethal heat, or knockdown of heat shock factor1 (HSF1), then PS-341-induced cell damage was examined by different methods. Similar experiments were also performed in HSF1+/+ and HSF1–/– cells. HSP70 expression and HSF1 nuclear localization were compared between glioma and normal brain tissues.

Results

HSP level was upregulated mediated by HSF1 when glioma cells were treated with PS-341. PS-341-mediated cell damage could be significantly augmented by HSP inhibition. Furthermore, HSP70 expression and HSF1 nuclear localization were much more abundant in gliomas than in normal brain tissues.

Conclusions

Our results demonstrated that HSP70 impaired cell death induced by PS-341 in glioma cells. Administration of PS-341 in combination with either HSP70 inhibitor or HSF1 knockdown may act as a new approach to treatment of glioma.

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Title: Inhibition of Heat Shock Protein Response Enhances PS-341-Mediated Glioma Cell Death
Authors: Yaohua Liu, MD, PhD
Tianhu Zheng, PhD
Shiguang Zhao, MD, PhD
Huailei Liu, MD
Dayong Han, MD
Yunbo Zhen, MD, PhD
Dongxiao Xu, MD
Yu Wang, MD
Hongyu Yang, MD
Guang Zhang, MD
Chunlei Wang, MD
Jianing Wu, MD
Yuanzhu Ye, MD
Publication date: 01-07-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue Special Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-1881-2

2024 ASCO Annual Meeting

Springer Medicine

Inhibition of Heat Shock Protein Response Enhances PS-341-Mediated Glioma Cell Death

Abstract

Background

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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