Administration of a hypoxic cell sensitizer, 6-FP, enhance of radiation-induced apoptosis in human carcinoma

给予缺氧细胞敏化剂 6-FP，增强辐射诱导的人类癌症细胞凋亡

• 批准号: 21591619
• 负责人: SHIGEMATSU Naoyuki
• 金额: $ 2.91万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591619/
• 关键词: 放射線抵抗性; 低酸素細胞; ラジカル; 増感効果; 染色体解析; 増感遺伝子解析; 増感剤

Hypoxia governs cellular adaption to oxygen deficiency by regulating tumor-relevant genes involved in energy metabolism, angiogenesis, cell proliferation and apoptosis. Heterogeneity of tumor was investigated with respect to radiosensitizing efficiencies of a hypoxic cell sensitizer, 6-FP(6-formylpterin), a metabolite of folic acid. In contrast to apoptosis induced by extracellular H_2O_2, only a few studies have examined apoptosis induced by intracellular H_2O_2. Oxidative stress is known to induce many forms of apoptosis, and as its common mediator, intracellular reactive oxygen species play a cardinal role in oxidative stress-induced apoptosis. Here we used an intracellular H_2O_2 inducer, 6-FP, which is a member of the pterin family. Tumor cells and normal cells were treated with 6-FP before expose of X-ray and then irradiated. We collected the cells and colony efficiency and survival fraction were analyzed. The results showed that the tumor cells were higher colony efficiency than the normal cells, and the cells with both X-ray irradiation and 6-FP treatment were significantly lower survival rate. These results suggested that 6-FP may have radioprotective effect for the tumor cells and the incidated that 6-FP enhances the apoptosis by the radiation-induced and 6-FP may be effective use of the drug.

缺氧通过调节参与能量代谢、血管生成、细胞增殖和凋亡的肿瘤相关基因来控制细胞对缺氧的适应。本文研究了叶酸代谢产物6-甲酰基蝶呤（6-FP）对乏氧细胞的放射增敏作用。与细胞外H_2O_2诱导的细胞凋亡不同，细胞内H_2O_2诱导的细胞凋亡研究较少。氧化应激可诱导多种形式的细胞凋亡，细胞内活性氧作为氧化应激的共同介质，在氧化应激诱导的细胞凋亡中起着重要作用。本实验使用了一种细胞内H_2O_2诱导剂6-FP，它是蝶呤家族的一员。肿瘤细胞和正常细胞在X射线照射前用6-FP处理，然后照射。收集细胞，分析集落效率和存活分数。结果表明，肿瘤细胞集落形成率高于正常细胞，X射线照射和6-FP联合处理的细胞存活率明显降低。提示6-FP对辐射诱导的肿瘤细胞凋亡有一定的保护作用，6-FP可能是一种有效的药物。

项目成果

Impact of MRI-based Postimplant Dosimetric Assessment in Prostate Brachytherapy using Contrast-Enhanced T1 Weighted Images

使用对比增强 T1 加权图像进行基于 MRI 的植入后剂量评估对前列腺近距离治疗的影响

• DOI: 10.1016/j.brachy.2011.12.010
• 发表时间: 2012
• 期刊: Brachytherapy
• 影响因子: 1.9
• 作者: Toshio Ohashi;Tetsuo Momma;Shoji Yamashita;Katsumi Nagatsuma;Kunimitsu Kanai;Kazuhito Kitagawa;Shinichi Takahashi;Takashi Hanada;Atsunori Yorozu;Naoyuki Shigematsu
• 通讯作者: Naoyuki Shigematsu

Clinical evidence of particle beam therapy

粒子束治疗的临床证据

• 发表时间: 2012
• 期刊: Int J Clin Oncol
• 影响因子: 3.3
• 作者: Shigematsu N;Shiraishi Y;Seki S;Fukada J;Ohashi T
• 通讯作者: Ohashi T