Development of new treatments against malignant bone and soft tissue tumors by using bisphosphonate and ionizing radiation

使用双膦酸盐和电离辐射开发针对恶性骨和软组织肿瘤的新疗法

• 批准号: 23592196
• 负责人: MURATA Hiroaki
• 金额: $ 3.24万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592196/
• 关键词: 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

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).

用第三代双膦酸盐(BPS)和/或电离辐射(IR)联合或顺序作用于纤维肉瘤细胞，评价其抗肿瘤作用。BPS能显著增强IR诱导的细胞凋亡，尤其是在细胞再用BPS处理后再用IR处理。因此，我们评估了BPS和IR序贯治疗的详细机制。细胞周期中对辐射最敏感的G2和M期细胞在低浓度的BPS作用下未见增加。而与辐射适应性抵抗相关的Akt、ERK1/2和NF-B蛋白在3Gy射线照射后短时间内表达增加，这种表达可被低浓度的BPS抑制，从而阻断小GTP酶的预烯基化。这种顺序处理还增加了活性氧物种(ROS)的生成。

项目成果

線維肉腫細胞株に対するゾレドロン酸と放射線の併用による細胞内シグナル伝達経路への影響の検討

唑来膦酸与放射线联用对纤维肉瘤细胞系细胞内信号转导途径影响的研究

• 发表时间: 2012
• 作者: 中田 浩史;中村 篤志;亀井 節也;藤渕 剛次;木谷 彰岐;三浦 裕正;宮崎 龍彦;坂山 憲史;小藤和孝,堀井基行,村田博昭,松井隆明,堀江直行,澤井泰志,久保俊一
• 通讯作者: 小藤和孝,堀井基行,村田博昭,松井隆明,堀江直行,澤井泰志,久保俊一

Zoledronic acid significantly enhances radiation-induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling

• DOI: 10.3892/ijo.2012.1735
• 发表时间: 2013-02-01
• 期刊: INTERNATIONAL JOURNAL OF ONCOLOGY
• 影响因子: 5.2
• 作者: Koto, Kazutaka;Murata, Hiroaki;Fushiki, Shinji
• 通讯作者: Fushiki, Shinji

Combined effects of the Third-Generation Bisphosphonate and Radiation on Fibrosarcoma Cells

第三代双膦酸盐和放射线对纤维肉瘤细胞的联合作用

• 发表时间: 2012
• 作者: Koto K;Murata H;Sakabe T;Matsui TA;Horie N;Sawai Y;Ashihara E;Kimura S;Maekawa T;Fushiki S;Kubo T
• 通讯作者: Kubo T

線維肉腫細胞株に対する第3世代ビスフォスフォネートと放射線の併用による抗腫瘍効果の検討

第三代双膦酸盐联合放射治疗纤维肉瘤细胞系的抗肿瘤作用研究

• 发表时间: 2011
• 作者: 松原孝夫;楠崎克之;中村知樹;浅沼邦洋;松峯昭彦;須藤啓広．;小藤和孝，村田博昭，坂部智哉，松井隆明，堀江直行，澤井泰志，久保俊一
• 通讯作者: 小藤和孝，村田博昭，坂部智哉，松井隆明，堀江直行，澤井泰志，久保俊一

The third-generation bisphosphonate shows combined effects with anti-tumor drugs in human fibrosarcoma cells

第三代双膦酸盐在人纤维肉瘤细胞中显示出与抗肿瘤药物的联合作用

• 发表时间: 2013
• 作者: Murata H;Koto K;Sawai Y;Matsui TA;Horie N;Fushiki S;Kimura S;Maekawa T;Horii M;Kubo T
• 通讯作者: Kubo T