Heat shock protein90 as a molecular target for therapy in oral squamous cell carcinoma: Inhibitory effects of 17‑DMAG and ganetespib on tumor cells.

Abstract

Heat shock protein90 (HSP90) expression is upregulated in numerous types of cancer. However, its role as a candidate for molecular targeted therapy in oral squamous cell carcinoma (OSCC) cells is poorly understood. In the present study, a common upstream search was performed using molecular network analysis software for proteins with expression abnormalities that were found in a proteomic analysis of six OSCC cell lines. HSP90 was identified as a target protein. In clinical samples, high frequencies of HSP90‑high expression were detected via immunohistochemistry (26/58;45%). Furthermore, the HSP90 expression status was associated with cervical lymph node metastasis (P=0.015). Furthermore, the potential of HSP90 as a candidate for molecular targeted therapy in OSCC cells was investigated using the HSP90 inhibitors 17‑dimethylaminoethylamino‑17‑demethoxygeldanamycin (17‑DMAG) and ganetespib. KON cells, which strongly express HSP90, were treated with the HSP90 inhibitors. The numbers of living cells in the 17‑DMAG and ganetespib‑treated groups were lower than those in the non‑treated group. The cells treated with the inhibitors demonstrated reduced cell viability and migration, and this was associated with markedly decreased levels of the HSP90 target proteins EGFR, phospho‑EGFR, phospho‑MEK and phospho‑MAPK in the treated groups compared with the non‑treated group. To the best of our knowledge, this was the first study to investigate the effects of 17‑DMAG and ganetespib on OSCC cells. The present results indicated the potential of HSP90 as a useful candidate for molecular targeted therapy in OSCC. However, additional studies with larger sample sizes are required to confirm these findings.