Zoledronic acid as an antimetastatic agent for different human tumor cell lines

Abstract

Background: Zoledronic acid effectively reduces skeletal events in patients with metastatic disease. The results of pre-clinical and emerging clinical data suggest an additional activity of zoledronic acid as an antitumor agent, interfering with the growth and dissemination of malignant cells. However, the mechanisms by which zoledronic acid impairs tumor progression are practically unknown. In the present study, we aimed to investigate the impact of zoledronic acid on invasion and colony formation ability of different human tumour cell lines.

Materials and methods: Human ovarian (SKOV3), colonic (HCT116), endometrial (HEC1A and Ishikawa) and breast cancer (MCF-7, MDA-MB-231, HCC1937, SKBR3 and T47D) cell lines were treated with different concentrations (10-100 μM) of zoledronic acid and analyzed using 3D assays to test their invasiveness and their ability to grow anchorage-independently, both hallmarks of aggressive tumor cell behavior.

Results: The most intense effect of the drug on tumor invasion was observed on MDA-MB-231 cells, but at high concentrations HEC1A, SKOV3 and SKBR3 cells also exhibited reduced invasion capacity. We also found a significant reduction of colony formation under zoledronic acid treatment in MCF-7, T47-D, HCT116, Ishikawa, HEC1A and SKOV3 cells.

Conclusion: Zoledronic acid presents an interesting potential for use as anti-metastatic agent for different solid tumor types, affecting relevant steps of tumor dissemination.

Keywords: 3D culture assays; Zoledronic acid; invasion; metastasis.