Application of NO generating agents as radiosensitizer and their modes of action.

NO发生剂作为放射增敏剂的应用及其作用方式。

• 批准号: 13470181
• 负责人: MATSUMOTO Hideki
• 金额: $ 7.23万
• 依托单位: Faculty of Medical Sciences, University of Fukui
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470181/
• 关键词: SCC; NSCLC; Radiotherapy; Hyperthermia; Drug for angina pectoris; p53; Hsp70; Apoptosis; apoptopsis; 放射線治療; 温熱療法; NOラジカル発生剤; バイスタンダー効果; Hsp72; 放射線; Nitric oxide; Nitric oxide発生剤; 放射線感受性; 細胞間シグナル伝達系; アポトーシス

We examined effects of a nitric oxide-generating agent, isosorbide dinitrate(ISDN), which is a quite popular drug for angina pectoris, on radiotherapy and hyperthermia to cancer cells in vifro and in vivo from an aspect of p53 functions.Transplantable p53-deficient human non-small cell lung cancer(NSCLC) H1299 cells were transfected with a vector carrying wild-type, mutant p53 gene or a neomycin-resistant gene(neo)alone as a control.Radiosensitivity and thermosensitivity at 44℃ of these transfectants in vitro was increased with ISDN (0.3 mM) in a p53-independent manner, although ISDN revealed no cytotoxicity at 37℃ in vitro. Western blot analysis indicated that the increase of thermosensitivity was partially due to a stimulation of decay of heat-induced Hsp72.Growth delay of these transplanted tumors after irradiation at 10 Gy or heating at 43℃ in vivo was enhanced with ISDN (0.3 mM) regardless of their p53 gene status, although lSDN revealed no effect on tumor growth.Immunohistochemical analysis(TUNEL method) indicated that the enhancement of tumor growth delay was partially due to induction of p53-independent apoptosisin both cases.These findings suggested that a p53-independent apoptosis induced an efficient cell killing and tumor growth delay by combined treatment with radiation or hyperthermia and ISDN.

我们检查了一氧化氧化物生成剂，异糖二酸（ISDN）的影响，它是一种非常流行的型心绞痛的药物，对p53函数的VIFRO和VIVO中的癌细胞对癌细胞的放射疗法和高温对癌细胞的影响。载体携带野生型，突变体p53基因或单独的抗新霉素基因（NEO）作为对照。在P53独立的方式中，ISDN（0.3 mm）在ISDN（0.3 mm）中增加了这些转化体的标准敏感性和热敏性，尽管ISDN中没有发现cytotoxientient cytotoxientient cytotoxicient fatro。蛋白质印迹分析表明，热敏性的增加部分是由于热诱导的HSP72的刺激。Hsp72。在10 Gy辐射后这些移植肿瘤的增长延迟或在43°在体内加热时，通过ISDN（0.3 mm）增强了体内（0.3 mm），尽管没有p53 Gene的状态，但lsd a揭示了tumer的效果（均未效应图）。方法）表明，肿瘤生长延迟的增强部分是由于两种情况诱导了p53非依赖性凋亡。这些发现表明，p53独立的凋亡通过与辐射或高温疗法和ISDN的联合处理来诱导有效的细胞杀伤和肿瘤生长延迟。

项目成果

Takahashi, A.et al.: "Radiation response of apoptosis in C57BLJ6N mouse spleen after whole-body irradiation."Int.J.Radiat.Biol.. 77. 939-945 (2001)

Takahashi, A. 等人：“全身照射后 C57BLJ6N 小鼠脾脏细胞凋亡的辐射反应。”Int.J.Radiat.Biol.. 77. 939-945 (2001)

Takahashi, A., 他8名: "Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body irradiation."Int.J.Radiat.Biol.. 77. 939-945 (2001)

Takahashi, A. 和其他 8 人：“全身照射后 C57BL/6N 小鼠脾脏细胞凋亡的辐射反应。”Int.J.Radiat.Biol.. 77. 939-945 (2001)

Shao, C.L.他4名: "Nitric oxide-mediated bystander effect induced by heavy-ions in human salivary gland tumour cells"Int.J.Radial.Biol.. 78. 839-844 (2002)

Shao, C.L. 等 4 人：“人唾液腺肿瘤细胞中重离子诱导的一氧化氮介导的旁观者效应” Int.J.Radial.Biol.. 78. 839-844 (2002)

Ohtsubo, T., 他7名: "Acidic environment modifies heat-or radiation-induced apoptosis in human maxillary cancer cells"Int J Radiation Oncol. Biol. Phys.. 49. 1391-1398 (2001)

Ohtsubo, T. 和其他 7 人：“酸性环境改变了人类上颌癌细胞中热或辐射诱导的细胞凋亡”Int J Radiation Oncol. 49. 1391-1398 (2001)

Matsumoto, H.et al.: "Intercellular signaling mediated by nitric oxide in glioblastoma cells."Method.Enzymol.. 359. 280-286 (2002)

Matsumoto, H.等人：“胶质母细胞瘤细胞中一氧化氮介导的细胞间信号传导。”Method.Enzymol.. 359. 280-286 (2002)