Zoledronic Acid and Leuprorelin Acetate, Alone or in Combination, Similarly Reduce Proliferation and Migration of Prostate Cancer Cells In Vitro

We studied the effects of zoledronic acid (ZA) and leuprorelin acetate (LA) separately and combined on a human cell line derived from a bone metastasis of prostatic adenocarcinoma (PC3). In particular, we focused on the effects that drugs given singularly or in association may play on tumor evolution and metastatization. Cell proliferation, 2D- and 3D-migration were studied in basal conditions and under attractive stimuli exerted by bone marrow mesenchymal stem cells (BM-MSC). Either drug decreased PC3 proliferation, though ZA was much more cytotoxic than LA. However, LA cytotoxic concentrations are higher than those usually reached in vivo. Subtoxic concentration of either drug inhibited migration especially under BM-MSC medium stimuli via an Akt-dependent mechanism. The capability of either drug to inhibit cellular migration is in line with their well-known effect in limiting metastatization. Intriguingly, no additive effect on the antiproliferative activity or in hindering migration is observed when the drugs are administered concomitantly, compared to the effects of each drug alone.