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锌酞菁磺酸盐光敏剂在人结肠(DLD-1)和肺(A549)癌细胞(体外)中的定位和光毒性效应。

Localization and phototoxic effect of zinc sulfophthalocyanine photosensitizer in human colon (DLD-1) and lung (A549) carcinoma cells (in vitro).

机构信息

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.

出版信息

Photodiagnosis Photodyn Ther. 2012 Mar;9(1):52-9. doi: 10.1016/j.pdpdt.2011.08.006. Epub 2011 Sep 16.

Abstract

BACKGROUND

Photodynamic therapy (PDT) is a therapeutic modality used for treating cancerous cells. It has been previously shown that mixed sulfonated metallophthalocyanine complex, zinc sulfophthalocyanine (ZnPcS(mix)) is effective in destroying lung cancer cells. This study aimed to determine subcellular localization of ZnPcS(mix) and its effect on two cancer cell lines.

METHODS

ZnPcS(mix) was activated at a wavelength of 680 nm with 5 J/cm². Colon (DLD-1) and lung (A549) cancer cell lines were used. Subcellular localization of ZnPcS(mix) was determined by fluorescence microscopy. Toxicity of PS alone and combination of light and PS (PDT) was determined by cell morphology, viability, proliferation and cytotoxicity. Cells which received no irradiation (0 J/cm²), irradiation alone (5 J/cm²) or treated with PS alone (no irradiation) served as controls.

RESULTS

ZnPcS(mix) localized in both lysozomes and mitochondria in both A549 and DLD-1 cells. A549 cells treated with PDT showed a significant decrease in viability and proliferation in all PS concentrations used, while in DLD-1 cells a significant decrease was seen with concentrations of 10, 20 and 40 μM. In absence of light, ZnPcS(mix) did not result in cellular toxicity in A549 cells whereas in DLD-1 cells it resulted in a reduction in cell proliferation only at a concentration of 40 μM.

CONCLUSION

ZnPcS(mix) was effective in inducing cell death in both cell lines when localized in vital organelles such mitochondria and lysozomes which are essential for cell functioning. Photoactivated ZnPcS(mix) affected the cells at different concentration and yielded good therapeutic results in vitro.

摘要

背景

光动力疗法(PDT)是一种用于治疗癌细胞的治疗方法。先前已经表明,混合磺化金属酞菁配合物,锌磺化酞菁(ZnPcS(mix))在破坏肺癌细胞方面是有效的。本研究旨在确定 ZnPcS(mix)的亚细胞定位及其对两种癌细胞系的影响。

方法

ZnPcS(mix)在 680nm 波长下用 5 J/cm²激活。使用结肠(DLD-1)和肺(A549)癌细胞系。通过荧光显微镜确定 ZnPcS(mix)的亚细胞定位。PS 单独和光与 PS 的联合(PDT)的毒性通过细胞形态、活力、增殖和细胞毒性来确定。未接受照射(0 J/cm²)、仅照射(5 J/cm²)或单独用 PS 处理(无照射)的细胞作为对照。

结果

ZnPcS(mix)在 A549 和 DLD-1 细胞中的溶酶体和线粒体中均有定位。用 PDT 处理的 A549 细胞在使用的所有 PS 浓度下,活力和增殖均显著下降,而在 DLD-1 细胞中,在浓度为 10、20 和 40 μM 时,活力和增殖显著下降。在没有光的情况下,ZnPcS(mix)在 A549 细胞中不会导致细胞毒性,而在 DLD-1 细胞中,仅在浓度为 40 μM 时才会导致细胞增殖减少。

结论

当 ZnPcS(mix)定位于线粒体和溶酶体等对细胞功能至关重要的细胞器中时,它在两种细胞系中都能有效诱导细胞死亡。光激活的 ZnPcS(mix)在不同浓度下影响细胞,并在体外产生良好的治疗效果。

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