T. Yuasa, M. Nogawa, S. Kimura
Jan 15, 2005
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Clinical Cancer Research
Abstract
Purpose: Minodronic acid (YM529) is a third-generation nitrogen-containing bisphosphonate. Here, we have investigated the therapeutic efficacy of YM529 against renal cell cancer (RCC) alone or in combination with IFN both in vitro and in vivo . Experimental Design: One murine and eight human RCC cell lines were used for the in vitro studies and were subjected to a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Western blotting. Luciferase-labeled murine RCC cells (RENCA Luc ) were transplanted into the s.c. tissue or the renal subcapsule of syngeneic BALB/c mice. These mice were treated with YM529 and/or murine IFN and the growth of the cancer cells was monitored by an in vivo imaging system. Results: YM529 inhibited the growth of RCC cells in a dose- and time-dependent manner and enhanced the growth inhibitory potential of IFN in vitro . In the in vivo mouse models, YM529 did not markedly inhibit the RCC cell growth on its own but it augmented the anticancer effect of IFN ( P Conclusions: Our study suggests that YM529 may be a potent anticancer agent for RCC. The efficacy and safety of IFN plus YM529 as a therapy for RCC should be verified by early-phase clinical trials.