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新型磺胺卟啉 TBPoS-2OH 用于恶性黑素瘤的光动力疗法。

Novel sulfonamide porphyrin TBPoS-2OH used in photodynamic therapy for malignant melanoma.

机构信息

Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, 264003, Yantai, China.

Jiangsu College of Nursing, 9 Science and Technology Avenue, Huaian, 223005, Jiangsu, China.

出版信息

Biomed Pharmacother. 2021 Jan;133:111042. doi: 10.1016/j.biopha.2020.111042. Epub 2020 Dec 8.

Abstract

The application of photodynamic therapy (PDT) for the treatment of skin diseases has been receiving much attention. Here, we examined the anti-tumor effect of a novel porphyrin-based photosensitizer TBPoS-2OH in the malignant melanoma A375 and B16 cells. TBPoS-2OH has obvious cell photo-cytotoxicity, but it has low cell dark-cytotoxicity. Further research showed that TBPoS-2OH is enriched in lysosomes after being taken up by cells. Subsequently, the apoptotic rates were significantly increased in TBPoS-2OH-treated A375 and B16 cells. The specific mechanism may be that after receiving light stimulation, TBPoS-2OH could effectively increase the level of intracellular reactive oxygen species (ROS), thereby activating mitochondrial apoptosis pathway-related proteins in A375 and B16 cells. We found an increase in the content of cytochrome C in the cytoplasm, and the levels of related proteins, such as cleaved caspase-3, cleaved caspase-9, and cleaved PARP1, were significantly increased in TBPoS-2OH-treated cells. These results indicated that the new compound TBPoS-2OH could be developed and become an alternative drug for the treatment of melanoma. Some reference ideas for the development of new photosensitizers are also provided.

摘要

光动力疗法(PDT)在皮肤病治疗中的应用受到了广泛关注。在这里,我们研究了新型卟啉类光敏剂 TBPoS-2OH 在恶性黑色素瘤 A375 和 B16 细胞中的抗肿瘤作用。TBPoS-2OH 对细胞具有明显的光细胞毒性,但暗细胞毒性较低。进一步的研究表明,TBPoS-2OH 被细胞摄取后在溶酶体中富集。随后,TBPoS-2OH 处理的 A375 和 B16 细胞的凋亡率显著增加。其特定机制可能是,TBPoS-2OH 在接收到光刺激后能够有效增加细胞内活性氧(ROS)的水平,从而激活 A375 和 B16 细胞中线粒体凋亡途径相关蛋白。我们发现细胞质中细胞色素 C 的含量增加,并且 TBPoS-2OH 处理的细胞中相关蛋白(如裂解的 caspase-3、裂解的 caspase-9 和裂解的 PARP1)的水平显著增加。这些结果表明,新型化合物 TBPoS-2OH 可被开发成为治疗黑色素瘤的替代药物。本研究还为新型光敏剂的开发提供了一些参考思路。

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