HSP90 inhibitor NVP-AUY922 induces cell apoptosis by disruption of the survivin in papillary thyroid carcinoma cells

Heat shock protein 90 (HSP90) is a molecular chaperone required for maintaining the stability and function of signal proteins that plays an important role in promoting the growth and survival of cancer cells. The incidence of papillary thyroid carcinoma (PTC) has been increasing in recent years. The effect of the novel non-geldanamycin HSP90 inhibitor NVP-AUY922 on apoptosis of papillary thyroid carcinoma cells has not been investigated. The influence of AUY922 on the survival of PTC cell lines K1 and IHH4 was evaluated. Cell viability was determined by cell counting kit method. Cell apoptosis was assessed by flow cytometry and western blotting and the potential mechanism was evaluated by western blotting and immunoprecipitation. Overexpression plasmid was transfected by Lipofectamine 2000 method. In K1 and IHH4 cell lines, after the treatment of AUY922, cell viability decreased, and the proportion of apoptosis cells increased. AUY922 caused the cleavage of PARP and caspase-3 proteins, and altered expression of survivin, which was a client protein of HSP90. In AUY922-treated cells, overexpression of survivin attenuated growth inhibition and cell apoptosis. The results indicate that AUY922 induces apoptotic cell death in PTC cells. Moreover, our findings demonstrate that AUY922 induced apoptosis by downregulating the expression of survivin protein in PTC cells.