Introduction and Objective: Originally, BPs were developed as a drug for bone diseases, However, recent studies demonstrated that the 3rd generation nitrogen-containing bisphosphonates (BPs) induce apoptosis in not only osteoclasts, but also several types of cancer cells and have an anti-cancer activities.In the present study, we investigated theeffects of NBPs on the growth of renal cancer cells.Methods: 1) BPs: incadronate (IC) and zoledronic acid (Zol).2) RCC cells: ACHN, LUS-M (established in our laboratory from human clear cell RCC, grade 2) 3) Cellgrowth assay: Cells were incubated with or without BP (IC: 0.1mM-0.1 M, Zol: 30 M-0.1 M) for 5 days.The viable cell number was determined by CellTiter96(R).4) Detection of apoptosis: LUS-M cells were cultured with or without BPs for 48h.Apoptotic cells were labelled using APOPercentage TM(R) and apoptotic index was determined.5) VEGF expression: Concentration of VEGF in the medium of cells was measured by ELISA.Result: At doses of 0.l mM-1 M, IC significantly inhibited the proliferation of LUS-M and ACHN cells (p<0.05).Thirty M-1 M of Zol also inhibited LUS-M cells (p<0.01-0.05).Apoptotic index was significantly higher in the IC or Zol-treated cells (p<0.05).Zol was stronger than IC in those activities.The BPs-induced growth inhibitory effect was circumvented by the addition of genranylgeraniol, which restores geranylgeranylation.Docetaxel enhanced the growth inhibitory effect of Zol, even when using low concentration of Zol (10nM).Concentration of VEGF in the conditioned medium of BPs-treated cells was significantly lower than that of control (p<0.01-0.05).Conclusions: NBPs have anti-cancer activities against renal cancer cells and the inhibition of geranylgeranylation may be associated with this antineoplastic action.Since docetaxel enhanced inhibitory effect of Zol, combination with docetaxel reduced the required concentrations of BPs and may exert anticancer activities in cancer cells in not only bone but in extra-bone tissues where concentrations of BP are low.In addition to direct anti-cancer activities, BP may have indirect anti-cancer activity by inhibition of angiogenesis.Exploring the anti-cancer mechanisms of BPs may provide a novel clue for the development of renal cancer treatments.