Development of a novel therapy for hormone-refractory prostate cancer

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RESEARCH RESULTS Fibroblast growth factor receptor 2 (FGFR2) is a receptor-type tyrosine kinase that has a growth inhibitory effect on hormone-refractory prostate cancer. To investigate the synergistic effects of radiation and an anticancer agent with FGFR2 in hormone-refractory human prostate cancer cells, a hormone-refractory human prostate cancer cell line, PC3, was transfected with FGFR2. The effects of radiation or docetaxel on cell cycle and apoptosis were evaluated by flowcytometry and Annexin affinity assay, respectively.Expression of FGFR2 in PC3 cells resulted in growth suppression in vitro and reduced tumor formation in vivo concurrent with increased cellular differentiation and apoptosis. Four to 8 Gy of radiation further decreased the number of colonies in transfected PC3 cells. Annexin affinity assay revealed that 8 Gy of radiation caused significant apoptosis for transfected PC3 cells. Also, at 24 hours after 8 Gy of radiation, proportion of G2/M phase was significantly higher in the transfected PC3 cells than in Mock cell. Docetaxel showed similar effects on the transfected PC3 cells.These results indicate that radiation and docetaxel enhance the growth-suppressive activity of FGFR2 in hormone-refractory human prostate cancer cells. Combination of FGFR2 with radiation or docetaxel may provide a new avenue for gene therapy of hormone-refractory prostate cancer.