Inhibitory effects of zoledronic acid on cell proliferation and invasion in human nasopharyngeal carcinoma cell line HNE1

Abstract

To explore the in vitro anti-tumor effects of zoledronic acid on cell proliferation and invasion in human nasopharyngeal carcinoma cell line HNE1. The cytotoxic effects of zoledronic acid on HNE1 cells were detected by MTT assay, invasion of HNE1 cells by Transwell assay, secretion of (vascular endothelial growth factor)VEGF by (enzyme-linked immunosorbent assay) ELISA and the activities of MMP (matrix metalloproteinase) 2 and MMP9 by gelatine zymography. And the expressions of mRNA and proteins of MMP2, MMP9 and VEGF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. After a treatment of zoledronic acid at 2.5, 5, 10, 20 and 40 mol/L for 48 h or 72 h, the highest inhibition rate of proliferation at approximately 50% was observed in the 40 mol/L group after 72 h. The inhibitory effect was not in a dose/time-dependent manner. After a 24-hour treatment of zoledronic acid at different concentrations (0, 10, 20 and 40 mol/L), the numbers of membrane-invading cells were 75.8 ± 2.6, 54.8 ± 5.4, 44.6 ± 6.4 and 38.6 ± 8.2 respectively (all P < 0.01). Gelatinase zymography demonstrated that the activities of MMP2 and MMP9 were inhibited significantly only in cells treated at 0 µmol/L. After a 24-hour exposure to zoledronic acid at 0, 10, 20 and 40 µmol/L, the concentrations of VEGF in supernatant were (5264 ± 89), (4626 ± 30), (4155 ± 40) and (1908 ± 171) g/L respectively (all P < 0.01). The expressions of mRNA and protein of MMP2, MMP9 and VEGF were down-regulated. Zoledronic acid can inhibit the in vitro proliferation and invasion of HNE1 cell through suppressing the secretion of VEGF, the activities of MMP2 and MMP9 and the expressions of VEGF, MMP2 and MMP9.