Zoledronic acid effects interleukin-6 expression in hormone-independent prostate cancer cell lines

Abstract

Objective: To investigate the inhibitory effects of zoledronic acid (ZA) on tumor related growth factor IL-6 in hormone resistant prostate cancer cell lines. The association between apoptosis and IL-6 inhibition was also assessed.

Materials and methods: PC-3 and DU145 cell lines were treated with different concentrations of ZA (1-100 microM) at various intervals (24-72 h.). The cell viability was investigated by XTT assay and apoptotic effect was evaluated by cell death detection ELISA kit. Caspase 3/7 activity assay was performed to confirm apoptosis. IL-6 levels were measured by ELISA in the supernatant, and these data were also confirmed by IL-6 mRNA analysis using RT-PCR.

Results: PC-3 and DU145 cell lines were sensitive to ZA mediated cytotoxicity in a dose- and time-dependent manner. However, the apoptotic effect was significantly different among PC-3 and DU145 cells (p<0.05). IL-6 secretion was significantly lower in both cell lines, compared to the untreated control cells (p<0.05). Although the increased inhibition of IL-6 secretion was associated with increased apoptosis in DU145 cells (p=0.002), there was no similar association for PC-3 cell line (p=0.347). When compared to the untreated controls, the number of cDNA copies was significantly lower in the ZA treated DU145 cell line at doses of 30 and 90 microM (p<0.05), suggesting a reduced expression of IL-6 mRNA.

Conclusion: ZA exhibited a time- and dose-dependent apoptotic effect on PC-3 and DU145 prostate cancer cell lines and this effect was associated with inhibited secretion of IL-6 in DU145 cell line.