Hypoxia attenuates Hsp90 inhibitor 17-DMAG-induced cyclin B1 accumulation in hepatocellular carcinoma cells

Cell Stress & Chaperones
Jianming ZhangXuemei Chen

Abstract

Hypoxia stress plays a pivotal role in tumor formation, proliferation, and invasion. Conventional chemotherapy is less effective in the hypoxia microenvironment of solid tumor. Heat shock protein 90 (Hsp90) is an important molecular chaperone in cancer cells and has been a pharmaceutical target for decades. However, Hsp90 inhibitors demonstrate limited effect on solid tumor and the mechanism underlying is not clear. To determine whether hypoxia impairs the therapeutic effect of Hsp90 N-terminal inhibitor, 17-demethoxygeldanamycin hydrochloride (17-DMAG), in live cancer cells, we measured cell proliferation and cell cycle distribution. Cell proliferation assay indicates that hypoxia obviously promotes the proliferation of HepG2 and Huh7 cells after 24, 48, and 72 h and impairs 17-DMAG-induced G2/M arrest in liver cancer cells. As a client protein of Hsp90, cyclin B1 is critical for the transition from G2 to M phase and is related to the prognosis of the patients. We further checked the cyclin B1 messenger RNA (mRNA) level, protein level, ubiquitination of cyclin B1, nuclear translocation, and degradation of cyclin B1 affected by hypoxia after 17-DMAG treatment. The results demonstrate that hypoxia decreases the transcription of ...Continue Reading

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Citations

Oct 30, 2016·Journal of Molecular Biology·Alexandra RehnJohannes Buchner
Apr 28, 2020·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Yongbin LuYana Bai
May 27, 2020·Journal of Cellular Physiology·Masoud Nouri-VaskehBehzad Baradaran
Mar 31, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hassan MellatyarNosratollah Zarghami

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Methods Mentioned

BETA
Antibody
flow cytometry
Infrared Imaging
co-immunoprecipitation
transfection
ubiquitination
PCR
confocal microscopy
florescence microscopy
nuclear translocation

Software Mentioned

SPSS
Mod fit LT
ImageJ

Related Concepts

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