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丹参酮 IIA 光动力诱导对脉络膜黑色素瘤细胞的高效抗癌作用。

Efficient Anticancer Effect on Choroidal Melanoma Cells Induced by Tanshinone IIA Photosensitization.

机构信息

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.

Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.

出版信息

Photochem Photobiol. 2021 Jul;97(4):841-850. doi: 10.1111/php.13399. Epub 2021 Feb 25.

Abstract

Tanshinone IIA (TanIIA) has multiple biological functions and already been clinically used to treat many cardiovascular diseases. TanIIA is a photoactive molecule and can be excited by light to generate TanIIA*. Generation of TanIIA* by TanIIA photosensitization indicates that TanIIA may serve as a photosensitizer to bring photodynamic damage to organisms. Therefore, human choroidal melanoma MUM-2B cell was chosen as a superficial tumor model and the photodynamic effect of TanIIA on tumor cells was evaluated in this study. The results showed that TanIIA photosensitization could generate singlet oxygen in noncellular system. MTT, clone formation and wound-healing assays showed that the survival and migration of MUM-2B cells could be efficiently inhibited by TanIIA photosensitization. And then, laser confocal microscope and flow cytometry were used to try to elucidate related mechanism. It was found that TanIIA could pass through cellular membrane and preferably accumulate in nucleus. TanIIA photosensitization could efficiently induce cell apoptosis and necrosis, increase intracellular ROS levels, decrease mitochondria membrane potential, and lead to cell cycle arrest in G2/M phase. Our findings indicate that TanIIA photosensitization can exert remarkable toxicity on choroidal melanoma cells.

摘要

丹参酮 IIA(TanIIA)具有多种生物学功能,已临床用于治疗多种心血管疾病。TanIIA 是一种光活性分子,可被光激发产生 TanIIA*。TanIIA 通过光致敏化产生 TanIIA*表明 TanIIA 可能作为光敏剂对生物体造成光动力损伤。因此,本研究选择人脉络膜黑色素瘤 MUM-2B 细胞作为浅层肿瘤模型,评估 TanIIA 对肿瘤细胞的光动力效应。结果表明,TanIIA 光致敏化可在非细胞体系中产生单线态氧。MTT、克隆形成和划痕愈合实验表明,TanIIA 光致敏化可有效抑制 MUM-2B 细胞的存活和迁移。然后,利用激光共聚焦显微镜和流式细胞术试图阐明相关机制。结果发现,TanIIA 可穿透细胞膜,并优先聚集在细胞核内。TanIIA 光致敏化可有效诱导细胞凋亡和坏死,增加细胞内 ROS 水平,降低线粒体膜电位,导致细胞周期停滞在 G2/M 期。我们的研究结果表明,TanIIA 光致敏化对脉络膜黑色素瘤细胞具有显著的毒性作用。

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