2006 Fiscal Year Final Research Report Summary
Development of a novel therapy for hormone-refractory prostate cancer
| Project/Area Number |
17591679
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
MATSUBARA Akio Hiroshima University, Graduate School of Biomedical Science, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (10239064)
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| Co-Investigator(Kenkyū-buntansha) |
MITA Koji Hiroshima University, Hospital, Assistant Professor, 病院・講師 (70304425)
MISHIMA Jun Hiroshima University, Graduate School of Biomedical Science, Research Associate, 大学院医歯薬学総合研究科, 助手 (20397962)
SEKI Mitsuhiro Hiroshima University, Graduate School of Biomedical Science, Research Associate, 大学院医歯薬学総合研究科, 助手 (80372697)
HASEGAWA Yasuhisa Hiroshima University, Hospital, Research Associate, 病院・助手 (90403568)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Fibroblast growth factor / Fibroblast growth factor receptor / Tyrosine kinase / Prostate cancer / Hormone refractory / Hormone refractory / Radiation / Gene therapy |
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| Research Abstract |
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.
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