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5-氨基乙酰丙酸及其己酯对几种细胞系的光动力效应。

Photodynamic effects of 5-aminolevulinic acid and its hexylester on several cell lines.

作者信息

Wu Shu-Min, Ren Qing-Guang, Zhou Mi-Ou, Wei Yi, Chen Ji-Yao

机构信息

Department of Physics, Fudan University, Shanghai 200433, China.

出版信息

Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2003 Jul;35(7):655-60.

Abstract

5-aminolevulinic acid (ALA) and its hexyl-ester (He-ALA) has shown promising results in photodynamic detection and therapy of tumors. In this work, the photodynamic effects of ALA and He-ALA on neuroblastoma cells, hepatoma cells and fibroblast cells were comparatively studied. With the detection of fluorescence emission spectra, protoporphyrin IX (PpIX) induced by ALA or He-ALA was observed in these three cell lines. Confocal laser scanning microscope showed the diffuse PpIX fluorescence in cytoplasm of neuroblastoma cells. The kinetics of PpIX accumulation were different in these three kinds of cells. The PpIX content in hepatoma cells and fibroblast cells continuously increased with the incubation time of drugs until 12 h, while in neuroblastoma cells the PpIX content saturated around 8 h after incubation with ALA or He-ALA. In addition, the PpIX concentration in neuroblastoma cells was obviously higher than that in hepatoma cells and fibroblast cells, indicating that the PpIX production is cell line dependent. When incubated with ALA and irradiated with light, near 90% neuroblastoma cells were destroyed, while for hepatoma cells and fibroblast cells the death rate was around 50%. The results demonstrate that neuroblastoma cells are more sensitive to ALA-PDT and the neuro-tumor cells may be well suited for the treatment of ALA mediated photosensitization. Comparing to ALA, He-ALA can reach the similar results concerned PpIX production and PDT damaging in all three kinds of cells but with 10 times lower incubation concentration, demonstrating that He-ALA has higher efficiency than ALA on inactivation of cancer cells in vitro.

摘要

5-氨基乙酰丙酸(ALA)及其己酯(He-ALA)在肿瘤的光动力检测与治疗中已显示出有前景的结果。在本研究中,对ALA和He-ALA对神经母细胞瘤细胞、肝癌细胞和成纤维细胞的光动力效应进行了比较研究。通过检测荧光发射光谱,在这三种细胞系中观察到了由ALA或He-ALA诱导产生的原卟啉IX(PpIX)。共聚焦激光扫描显微镜显示神经母细胞瘤细胞胞质中存在弥漫性的PpIX荧光。这三种细胞中PpIX积累的动力学情况不同。肝癌细胞和成纤维细胞中的PpIX含量随着药物孵育时间的延长持续增加,直至12小时,而在神经母细胞瘤细胞中,用ALA或He-ALA孵育约8小时后PpIX含量达到饱和。此外,神经母细胞瘤细胞中的PpIX浓度明显高于肝癌细胞和成纤维细胞,表明PpIX的产生具有细胞系依赖性。当用ALA孵育并照射光时,近90%的神经母细胞瘤细胞被破坏,而肝癌细胞和成纤维细胞的死亡率约为50%。结果表明神经母细胞瘤细胞对ALA介导的光动力疗法更敏感,神经肿瘤细胞可能非常适合ALA介导的光致敏治疗。与ALA相比,He-ALA在所有三种细胞中关于PpIX产生和光动力疗法损伤方面能达到相似的结果,但孵育浓度低10倍,这表明He-ALA在体外对癌细胞的灭活效率高于ALA。

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