Clinical and biological significances of heat shock protein 90 (Hsp90) in human nasopharyngeal carcinoma cells and anti-cancer effects of Hsp90 inhibitor

摘要

Nasopharyngeal carcinoma (NPC) is a malignant tumor in South China, characterized with high death rate. If untreated, NPC cells will be invasiveness and then spread to other tissues. In clinical practice, however, lack of early effective screening to prevent the NPC development. Therefore, candidate biomarker for detecting NPC is developing urgently. In current study, human NPC data and samples were collected for tests, followed by cell culture study. As results, Epstein-Barr virus (EBV)-based human NPC sections showed increased expressions of heat shock protein 90 (Hsp90), protein kinase B (AKT), and Hsp90 levels were positively expressed than those in cytokeratin 19 (CK19). The clinical data showed unchanged contents of blood cancer markers. In cell line study, Hsp90-treated cells (CNE1, 5-8 F) resulted in promoted cellular growth and proliferation. Additionally, proliferative proteins of cellular extracellular regulated protein kinase (Erk1/2), phospho-Erk1/2 (Thr202+Tyr204), B-cell lymphoma-2 (Bcl-2), AKT, phospho-AKT (Ser473), Ki-67 were up-regulated in Hsp90 treatments, while the apoptotic protease activating factor-1 (Apaf1) were down-regulated. Followed by treatment with Hsp90 inhibitor, the NPC cells exhibited inhibited cellular proliferation and growth, induced cell apoptosis, reduced proliferative proteins of Erk1/2, phospho-Erk1/2 (Thr202+Tyr204), AKT, phospho-AKT (Ser473), Bcl-2, Ki-67, and elevated Apaf1 expression. In conclusion, the current findings obtained from this study demonstrate that Hsp90 effectively promotes cell proliferation through activating carcinomatous ERK1/2, phospho-Erk1/2 (Thr202+Tyr204), AKT, phospho-AKT (Ser473) expressions in NPC cells. Briefly, Hsp90 may be a promising biomarker to screen NPC, including early stage.