The anti-tumor activity of zoledronic acid and synergistic effect of zoledronic acid combination with docetaxel on prostate cancer cell line PC-3 in vitro at clinically achievable concentrations

To observe the effect of zoledronic acid alone or combination with docetaxel in different concentrations on prostate cancer PC-3 cells in vitro. Cell morphology, MTT, flow cytometry method was used to observe this effect. Above 200 mu g/ml zoledronic acid significantly enhanced growth suppression (suppression ratio >= 44.5%, P< 0.05), apoptosis (apoptosis ratio >= 5.93%, P< 0.05). The combination of ZOL and DOC inhibited the proliferation of PC-3 cells significantly. The effect was dose-depended by ZOL with a certain dose of DOC. When the concentration of DOC was 10 ng/ml, the inhibition rate was 49.3%, 61.4% respectively after the treat with 200 mu g/ml ZOL or 400 mu g/ml ZOL. The inhibition rate could rise to 59.7%, 74.2% with 200 mu g/ml ZOL or 400 mu g/ml ZOL exposure combined with 100 ng/ml DOC. Flow cytometry showed G2 and S phase of PC-3 cells in 400 mu g/ml zoledronic acid were inhibited significantly more than the control group (P< 0.05) and G1 phase was less inhibitid (P< 0.05). This research validates that ZOL has the effect of inhibiting proliferation and inducing apoptosis of hormone refractory prostate cancer PC-3 cells. ZOL arrests the cell cycle to S phase, G2/M phase. These effects are dose-dependent. The combination of ZOL and docetaxel inhibites proliferation more than each drug alone, the effect of which is also dose-dependent and the two drugs have synergia anti-tumor effect on prostate cancer PC-3 cells in vitro.