FGF2 Accelerates the Development of Nasopharyngeal Carcinoma through Regulating Mitochondrial Apoptosis in BALB/c Mice in Vivo

Abstract

Background: Nasopharyngeal carcinoma (NPC) is a common malignancy originated from the nasopharynx superior mucosal epithelium. Fibroblast growth factor 2 (FGF2) has been proved to play a vital role in various cancers. The aim of this study is to explore the role of FGF2 in NPC development. Methods: RT-qPCR was applied to examine the mRNA level of FGF2 in NPC tissues and cells. The protein expression of FGF2, Ki-67, and mitochondrial apoptosis-related proteins [Bax, apoptotic protease activating factor-1 (Apaf-1), capase-7, caspase-9, and caspase-3] were determined by western blot. Cell proliferation, cell viability, the invasive ability and the apoptotic rate of NPC cells were measured using 5-Ethynyl-2′-deoxyuridine (EdU) assay, Cell Counting Kit-8 (CCK-8) assay, transwell invasion assay, and flow cytometry, respectively. In xenograft murine NPC model, the mice were divided into sh-NC and sh-FGF2 groups in the first animal experiment. Moreover, sh-NC, sh-FGF2, and sh-FGF2+sh-Apaf-1 groups were established in the second animal experiment. Tumor weight was calculated, and determination of Ca+ intracellular concentration in tumor tissues from mice was carried out using Fura-2 pentakis/acetoxymethyl (Fura-2/AM). Results: The elevated FGF2 levels were verified in NPC tissues and cells (p < 0.05), and knockdown of FGF2 suppressed cell invasion and proliferation, and enhanced cell apoptosis in NPC cells (p < 0.05). The results from the in vivo experiment demonstrated that FGF2 knockdown dramatically hampered tumor growth (p < 0.05), and increased mitochondrial apoptosis (p < 0.05) and Ca+ intracellular concentration (p < 0.05) in mice. In addition, we found that Apaf-1 knockdown reversed the effects of FGF2 downregulation on tumor growth, mitochondrial apoptosis, and Ca+ intracellular concentration (p < 0.05) in NPC mice. Conclusions: FGF2 knockdown exerted the inhibitory impacts on the development of NPC through regulating mitochondrial apoptosis.