The Hsp90 inhibitor SNX-2112 induces apoptosis of human hepatocellular carcinoma cells: the role of ER stress.

摘要: Heat shock protein 90 (Hsp90) has been predicted to be involved in hepatocellular carcinoma (HCC) therapy; however, the mechanisms of action remain elusive. SNX-2112 is an Hsp90 inhibitor showing broad antitumor activity. Here we aim determine role endoplasmic reticulum (ER) stress SNX-2112-induced apoptosis HCC cells. In general, three cells (i.e., HepG2, Huh7, and SK-Hep1) were used our experiments. The cell viability was determined by CCK-8 assay. analyzed using flow cytometry, laser scanning confocal microscopy (LSM) Western blotting. efficacy also evaluated a mouse xenograft model. We found that showed stronger inhibition on growth than 17-AAG, classical inhibitor. treatment led caspase-dependent apoptosis. Interestingly, decreased expression levels ER chaperone proteins calnexin immunoglobulin binding (BiP). It inhibited all sensors, namely, inositol-requiring gene 1 (IRE1), PKR-like kinase (PERK), activating transcription factor 6 (ATF-6) vitro and/or vivo. However, inducer tunicamycin strongly enhanced apoptosis, whereas IRE1 knockdown did not. Taken together, for first time indicated possible apoptotic pathways cells, raising possibility induction might favorable