2005 Fiscal Year Final Research Report Summary
The development of the novel genetherapy to enhance the radiation sensitivity.
| Project/Area Number |
17591250
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Radiation science
|
|---|
| Research Institution | Chiba Cancer Center (Research Institute) |
|---|
Principal Investigator |
NIMURA Yoshinori Chiba Cancer Center Research Institute, Division of Biochemistry, Post doctoral fellow, 生化学研究部, 研修生 (50345021)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAWATA Tetsuya Chiba University Graduate School of Medicine, Department of Radiology, Assistant professor, 大学院医学研究院, 講師 (60234077)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | Radiation sensitivity / Genetherapy |
|---|
| Research Abstract |
Ku80 is an important component of DNA double-strand breaks repairs, and Ku80 deficiency leads to extreme sensitivity to ionizing radiation. We studied whether radiation therapy combined with Ku80 silencing by small interfering RNA enhances radiation sensitivity in vitro and in vivo. Seven human cancer cell lines were transfected with Ku80 siRNA included in hemagglutinating virus of Japan envelope vector. H1299 cells were implanted on male BALB/C nu/nu nude mice treated with Ku80 siRNA and irradiation. The survival rate of cell lines transfected with Ku80 siRNA decreased by 10% to 26% with 2-Gy irradiation compared with untransfected cell lines. The gamma-H2AX phosphorylation-positive rates of Ku80 siRNA combined treatment 0.5 hour after irradiation in A549 cells and 6 hours in H1299 cells were significantly higher (77.6%, p=0.033 and 76.7%, p=0.026, respectively), compared with the groups not treated with siRNA. H1299 xenograft tumors treated with combined therapy decreased in volume and re-grew slowly compared with radiation alone. Our results indicate that combined therapy consisting of Ku80 siRNA and irradiation contributes to inhibited tumor growth and may be a novel strategy for cancer treatment.
|
