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The effect of a novel photodynamic therapy with glycoconjugated fullerene and ultraviolet A-1 irradiation against bladder cancer cells

糖缀合富勒烯和紫外线 A-1 照射的新型光动力疗法对膀胱癌细胞的作用

基本信息

批准号：
22791486
负责人：
IKEGAMI Yosuke
金额：
$ 2.58万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791486/
关键词：
癌光物性蛋白質

项目摘要

【Purpose】Photodynamic therapy(PDT) is an anticancer approach utilizing a light-absoring molecule and visible light irradiation to generate, in the presence of O^2, cytotoxic reactive oxygen species, which cause tumor ablation. Glycoconjugated fullerene (C60-glu) is a new photosensitizer which accumulates in malignant cells(Fig.1). Previously, we report that ultraviolet A-1(UVA-1) irradiation induced apoptosis occurs in a malignant cells rather than a normal cells. In this study, we investigated the effect of a novel PDT with C60-Glu and UVA-1 irradiation against bladder cancer cells. 【Material and Methods】Fullerene is considered a new class of carbon molecules. Fullerene discovered in 1985 is composed of 60 carbon atoms arranged in a soccer ball-like structure. Although fullerene is a well-known radical scavenger, it has excitation wavelengths in the ultraviolet A-1 region (340-400nm) and generates ROS effectively upon excitation. And, fullerene is not toxic in the dark. Three human bladder cancer cell lines (T24, 5637 and RT4) were used in this study. We analyzed these photocytotoxic effects by WST-1 assay or flow cytometric analysis. Next in vivo, we implanted in BALB/c-nu/nu male mice, and analyze the tumor growth by no treatment or PDT. 【Results and Discussion】We were able to observe the cytotoxic effect and apoptosis in all bladder cancer cell lines treated with only C60-gul or simple UVA-1 irradiation. But by these combination therapy, we observed a significant photocytotoxic effect and apoptosis. In vivo, this PDT suppressed the tumor growth. These studies indicated that PDT with C60-glu and UVA-1 was a new choice as a bladder cancer therapy.

【目的】光动力疗法（Photodynamic therapy，PDT）是一种利用光致发光分子和可见光照射，在O^2存在下产生细胞毒性活性氧，从而导致肿瘤消融的抗癌方法。糖共轭富勒烯（C60-glu）是一种新的光敏剂，在恶性肿瘤细胞中积累。以前，我们报道了紫外线A-1（UVA-1）照射诱导的凋亡发生在恶性细胞而不是正常细胞中。在这项研究中，我们研究了一种新的PDT与C60-Glu和UVA-1照射对膀胱癌细胞的作用。[材料与方法]富勒烯被认为是一类新的碳分子。1985年发现的富勒烯由60个碳原子组成，排列成足球状结构。虽然富勒烯是一种众所周知的自由基清除剂，但它的激发波长在紫外线A-1区（340- 400 nm），并在激发时有效地产生ROS。富勒烯在黑暗中是无毒的。本研究中使用了三种人膀胱癌细胞系（T24、5637和RT 4）。我们通过WST-1检测或流式细胞术分析这些光细胞毒性效应。接下来在体内，我们将其植入BALB/c-nu/nu雄性小鼠中，并在不治疗或PDT的情况下分析肿瘤生长。[结果与讨论] C60-gul和UVA-1单独照射对膀胱癌细胞株均有明显的细胞毒作用和细胞凋亡。但通过这些联合治疗，我们观察到了显著的光细胞毒性效应和细胞凋亡。在体内，这种PDT抑制肿瘤生长。这些研究表明，PDT联合C60-glu和UVA-1治疗膀胱癌是一种新的选择。