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

Hypoxia attenuates Hsp90 inhibitor 17-DMAG-induced cyclin B1 accumulation in hepatocellular carcinoma cells.
Cell Stress Chaperones. 2016 Jan 20;
Authors: Zhang J, Li H, Huang Z, He Y, Zhou X, Huang T, Dai P, Duan D, Ma X, Yin Q, Wang X, Liu H, Chen S, Zou F, Chen X
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. T...

Source: Cell Stress and Chaperones - January 20, 2016 Category: Cytology Authors: Zhang J, Li H, Huang Z, He Y, Zhou X, Huang T, Dai P, Duan D, Ma X, Yin Q, Wang X, Liu H, Chen S, Zou F, Chen X Tags: Cell Stress Chaperones Source Type: research