Zoledronic acid inhibits human nasopharyngeal carcinoma cell proliferation by activating mitochondrial apoptotic pathway

Abstract

We investigated the apoptosis-inducing effect of zoledronic acid in human nasopharyngeal carcinoma cell HNE-1 and explore the potential mechanism. Human nasopharyngeal carcinoma cell HNE-1 was exposed to various concentrations (0-40 μmol/L) of zoledronic acid. Cell proliferation was studied by an MTT assay. Cell apoptosis was analyzed by flow cytometry and TdT-mediated dUTP nick-end labeling (TUNEL) assay. Cell cycle was analyzed by flow cytometry. Gene expressions were investigated by quantitative real-time PCR, and protein expressions were investigated by Western blot. The results showed zoledronic acid decreased cell proliferation not in a time- or dose-dependent fashion. TUNEL assay, together with Annexin V/propidium iodide FACS analysis, confirmed the increase in apoptotic HNE-1 cells treated with zoledronic acid. Cell cycle analysis showed a larger number of treated cells occupied the S-phase. Quantitative RT-PCR and Western blot revealed that the pro-apoptotic genes, Bad, Bax, and Caspase-9, were upregulated in treated HNE-1 cells, whereas the anti-apoptotic gene, Bcl-2, was downregulated in both mRNA and protein levels. In conclusion, zoledronic inhibits human nasopharyngeal carcinoma cell proliferation by inducing apoptosis via the mitochondrial apoptotic pathway.