WWOX suppresses proliferation and induces apoptosis via G2 arrest and caspase 3 pathway in nasopharyngeal carcinoma cells

WWOX plays crucial roles in various tumors. However, so far, minimal research into the role of WWOX in the development of nasopharyngeal carcinoma (NPC) has been reported. The present study investigates the effects of WWOX overexpression on cell proliferation, migration, and invasion in human NPC cell line CNE1. Materials and

WWOX gene may be a novel target for gene therapy in NPC.

A lentiviral vector carrying WWOX was transfected into CNE1 cells. The mRNA abundances of WWOX, MMP9, E-cadherin and WWOX protein were detected using quantitative RT-PCR and Western blotting in the transfected cells compared with the control cells (cells transfected using the empty vector and untransfected cells), respectively. Cell proliferation rates were assessed by plate colony formation assays and methyl thiazolyl tetrazolium (MTT). Cell migration and invasion were tested through wound healing assays and/or transwell migration and invasion assays. Cell cycle progression and apoptosis assays were performed by flow cytometry. The protein abundances of activated fragments of caspase-3, cleaved caspase-3 and AKT, phosphorylated p-AKT (Ser473) were measured using Western blotting.

Overexpression of WWOX significantly inhibited cell proliferation, migration and invasion and induced apoptosis. Moreover, WWOX overexpression led to cell proliferation inhibition via induction of cell cycle arrest in G2/M phase. WWOX suppressed migration and invasion via downregulation of MMP9 and upregulation of E-cadherin. Meanwhile, WWOX could downregulate the phosphorylation of Akt protein kinase and upregulate cleavage of Caspase-3, contributing to inhibition of proliferation and promotion of apoptosis.