Project/Area Number |
23592196
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
MURATA Hiroaki 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (90360031)
|
Co-Investigator(Kenkyū-buntansha) |
KOTO Kazutaka 明治国際医療大学, 公私立大学の部局等, 講師 (50649340)
|
Co-Investigator(Renkei-kenkyūsha) |
MAEKAWA Taira 京都大学, 大学院医学研究科, 教授 (80229286)
KIMURA Shinya 佐賀大学, 医学部, 教授 (80359794)
ASHIHARA Eishi 京都薬科大学, 薬学部, 教授 (70275197)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | ビスホスフォネート / 軟部肉腫 / 放射線治療 / アポトーシス / 骨肉腫 / ビスホスホネート |
Research Abstract |
Fibrosarcoma cells were treated with third-generation bisphosphonate (BPs) and/or ionizing radiation (IR), together or sequentially, and the antitumor effects were assessed. BPs significantly enhanced IR-induced apoptosis, especially when cells were treated with BPs followed by IR. We therefore assessed the detailed mechanism of sequential treatment with BPs and IR. Cells in G2 and M phases, the most radiosensitive phases of the cell cycle, were not increased by low concentrations of BPs. However, the levels of expression of Akt, ERK1/2, and NF- B proteins, all of which are related to radioadaptive resistance, were increased within a short time after irradiation with 3 Gy, and this expression was inhibited by a low concentration of BPs, which blocked the prenylation of small GTPases. This sequential treatment also increased the generation of reactive oxygen species (ROS).
|