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金丝桃素和5-氨基乙酰丙酸诱导的原卟啉IX在非相干白光照射下对人子宫内膜癌细胞产生增强的光毒性。

Hypericin and 5-aminolevulinic acid-induced protoporphyrin IX induce enhanced phototoxicity in human endometrial cancer cells with non-coherent white light.

作者信息

Schneider-Yin Xiaoye, Kurmanaviciene Aida, Roth Marion, Roos Malgorzata, Fedier André, Minder Elisabeth I, Walt Heinrich

机构信息

Central Laboratory, Triemli Hospital, Zurich, Switzerland.

出版信息

Photodiagnosis Photodyn Ther. 2009 Mar;6(1):12-8. doi: 10.1016/j.pdpdt.2009.02.001. Epub 2009 Mar 16.

Abstract

BACKGROUND

The in vitro experiments described in this study were aimed at exploring a synergistic effect between 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) and hypericin. In a previous study, enhanced phototoxicity was observed in a patient during a clinical study on 5-ALA-based photodynamic tumor localization of breast cancer. This patient ingested a hypericin containing plant extract in parallel to orally applied 5-ALA.

METHODS

Human endometrial cancer cells (HEC-1A) were treated with 0.5mM of 5-ALA and 60 nM of hypericin, either separately or combined. Colony formation was assessed after illumination of the cells with both red (635 nm) and white light (400-800 nm) at a dose of 2.5 J/cm(2). Porphyrin metabolites were quantified by HPLC in cells treated with photosensitizers without subsequent illumination.

RESULTS

After white light illumination, cells treated with a combination of 5-ALA and hypericin had a significant reduction in colony formation compared with cells treated with 5-ALA only. No significantly enhanced toxicity was found with red light and the 5-ALA plus hypericin combination. In addition, cells treated with both 5-ALA and hypericin tended to produce more PpIX than cells treated with 5-ALA only.

CONCLUSIONS

This study demonstrated that treatment of endometrial cancer cells with both 5-ALA and hypericin followed by illumination with white light induced a significantly higher phototoxicity as revealed by colony formation. This setting which generated an in vitro effect similar to the patient's situation, might be applied in the future as an affordable and effective photodynamic therapy (PDT) modality.

摘要

背景

本研究中所描述的体外实验旨在探究5-氨基乙酰丙酸(5-ALA)诱导产生的原卟啉IX(PpIX)与金丝桃素之间的协同效应。在之前一项关于基于5-ALA的乳腺癌光动力肿瘤定位的临床研究中,观察到一名患者的光毒性增强。该患者在口服5-ALA的同时摄入了一种含有金丝桃素的植物提取物。

方法

将人子宫内膜癌细胞(HEC-1A)分别用0.5mM的5-ALA和60nM的金丝桃素处理,或二者联合处理。在用2.5J/cm²的红光(635nm)和白光(400 - 800nm)照射细胞后,评估集落形成情况。在用光敏剂处理但随后未进行照射的细胞中,通过高效液相色谱法对卟啉代谢产物进行定量分析。

结果

白光照射后,与仅用5-ALA处理的细胞相比,用5-ALA和金丝桃素联合处理的细胞集落形成显著减少。在红光和5-ALA加金丝桃素联合处理的情况下,未发现毒性显著增强。此外,与仅用5-ALA处理的细胞相比,同时用5-ALA和金丝桃素处理的细胞倾向于产生更多的PpIX。

结论

本研究表明,先用5-ALA和金丝桃素处理子宫内膜癌细胞,然后用白光照射,如集落形成所示,会诱导显著更高的光毒性。这种产生与患者情况相似的体外效应的设置,未来可能作为一种经济有效的光动力疗法(PDT)模式应用。

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