PPAR-γLigand Inhibits Nasopharyngeal Carcinoma Cell Proliferation and Metastasis by Regulating E2F2

Abstract

Purpose. Peroxisome proliferator-activated receptor-γ(PPAR-γ) is a nuclear hormone receptor with a key role in lipid metabolism. Previous studies have identified various roles of PPAR-γin cell cycle progression, cellular proliferation, and tumor progression. However, no report has described a role for PPAR-γin human nasopharyngeal carcinoma (NPC). Notably, some studies have reported a relationship between PPAR-γand E2F transcription factor 2 (E2F2), which has been identified as a regulator of cell cycle, apoptosis, and the DNA damage response. Notably, E2F2 has also been reported to correlate with a poor prognosis in patients with various malignancies.Methods. We used immunohistochemical (IHC) and western blot methods to evaluate PPAR-γand E2F2 expression and function in nonkeratinizing NPC and nasopharyngitis (NPG) tissue samples, as well as western blotting and CCK8 analyses in the NPC cell lines, CNE1 and CNE2.Results. We observed lower levels of PPAR-γexpression in nonkeratinizing NPC tissues compared with NPG tissues and determined an association between a low level of PPAR-γexpression with a more advanced tumor stage. Furthermore, strong E2F2 expression was detected in nonkeratinizing NPC tissues. We further demonstrated that rosiglitazone, a PPAR-γagonist, reduced E2F2 expression and proliferation in NPC cell lines.Conclusions. Our study results revealed a novel role for the PPAR-γ–E2F2 pathway in controlling NPC cell proliferation and metastasis.