Zoledronic acid inhibits hepatocellular carcinoma cells growth in vitro and in vivo

Abstract Background Growing preclinical data show zoledronic acid (ZOL) exhibits direct antitumor activity in various cancer cells. But the cytotoxic effects of ZOL on human hepatocellular carcinoma (HCC) cells has not been reported. In the present study, we investigate the influence of the ZOL on HCC in vitro and in vivo. Methods Cytotoxicity and cell cycles were assessed with a Sulforhodamine B colorimetric assay and flow cytometry, respectively. Expression levels of cell cycle phase-linked proteins have been examed. The effect of ZOL on HCC in vivo was explored by H22- s.c. and H22- i.p. mice model. Results ZOL inhibited the growth of SK-HEP-1 and H22 cells and induced S-phase arrest which may through lower down the expression of cdc2 protein and induce an upregulation of cyclin A. ZOL inhibited the growth of s.c tumors and increased the survival of mice with s.c tumors and i.p. tumors in vivo. Conclusion In conclusion, ZOL inhibits HCC cell growth in vitro and in vivo. These results support further study of ZOL in the management of HCC.