Hepatocyte growth factor suppresses tumor cell apoptosis in nasopharyngeal carcinoma by upregulating Bcl-2 protein expression

Hepatocyte growth factor (HGF) is a multifunctional cytokine, but cell apoptosis related to HGF in nasopharyngeal carcinoma (NPC) and the potential mechanisms involved have not yet been identified. In this study, we aimed at determining whether HGF is a potent inhibitor of cell apoptosis in NPC, and tried to find out which antiapoptotic or proapoptotic protein is involved in this process. A hundred and forty-seven cases of NPC and CNE-1, CNE-2 NPC cell line were collected. Expression of HGF, Bcl-2 and Bax in tumor tissues was investigated by immunohistochemical staining, and the apoptotic index was evaluated using the Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method in all of the NPC cases. NPC cells were treated with HGF (25 ng/ml), followed by an assay for cell viability and apoptosis, as well as by an expression analysis of Bcl-2 and Bax using immunostaining and Western blot. The presence of Epstein-Barr virus (EBV) was also detected in NPC cells using polymerase chain reaction (PCR) for Barn HI W fragment. In tumor cells, expression of HGF was strong in 51% (75/147) of the NPC cases. In stromal cells, expression of HGF was also strong in 78.9% (116/147) of the cases. Strong expression of HGF in tumor cells and stromal cells was significantly associated with decreased apoptotic index, advanced clinical stage, lymph node metastasis and high-expression of Bcl-2. In vitro, exogenous HGF was found to promote cell growth, to suppress cell apoptosis and to upregulate the expression of Bcl-2 in NPC cells without EBV infection. HGF is a potent inhibitor of cell apoptosis in NPC by upregulating Bcl-2 through both autocrine and paracrine EBV-independent pathways. HGF might be a potential marker for the prognosis of NPC. Crown Copyright (C) 2009 Published by Elsevier GmbH. All rights reserved.