Fibroblast growth factor receptor 2 (FGFR2) is thought to mediate an important signaling pathway between prostate epithelial cells and stromal cells for maintenance of homeostasis in normal prostate tissue. Abnormalities of FGFR2 have been shown in advanced
prostate cancer or
prostate cancer cell lines, and we previously demonstrated the
tumor-suppressive effects of the restoration of FGFR2IIIb in
prostate cancer cells. The aim of the present study was to determine whether FGFR2IIIb plays a role in the chemosensitivity of
castration-resistant
prostate cancer cells. A clonal line of PC-3 cells expressing FGFR2IIIb (PC-3R2IIIb) was established by transfection with an IRESneo2-expressing vector bearing FGFR2IIIb
cDNA. The effects of chemotherapeutic agents (
docetaxel,
cisplatin,
5-fluorouracil and
zoledronic acid) on cell viability and apoptosis were examined by MTT assay and western blot analysis, respectively. Expression levels of molecules that were markers of epithelial-to-mesenchymal transition and chemosensitivity-related
proteins were assessed by western blot analysis. Viability of the PC-3R2IIIb cells was significantly lower than that of the control PC-3 cells transfected with the vector alone (PC-3neo), and viability was further suppressed by treatment with chemotherapeutic agents, particularly
docetaxel. Induced expression of
caspase-3 was evident in the PC-3R2IIIb cells and was further enhanced by treatment with
docetaxel. Expression of
N-cadherin,
vimentin,
survivin and XIAP was lower in the PC-3R2IIIb cells than that in the PC-3neo cells. In contrast, expression of p21 was higher in the PC-3R2IIIb cells than that in the control PC-3neo cells. These data indicate that restoration of FGFR2IIIb in
castration-resistant
prostate cancer cells may reverse some of the epithelial-to-mesenchymal cell properties characteristic of
tumor cells and induce in part mesenchymal-to-epithelial transition properties. This together with enhancement of apoptotic pathways involving
caspase-3 may enhance chemosensitivity particularly to
docetaxel which is widely used in the treatment of
castration-resistant
prostate cancer.