新型席夫碱-硅（IV）酞菁配合物的合成与表征及其用于乳腺癌细胞系的光动力治疗。
Synthesis and characterization of novel Schiff base-silicon (IV) phthalocyanine complex for photodynamic therapy of breast cancer cell lines.
机构信息
Department of Medical Biology, Institute of Health Sciences, Karadeniz Technical University, Trabzon, Turkey.
Department of Chemistry, Faculty of Sciences, Karadeniz Technical University, Trabzon, Turkey.
出版信息
Photodiagnosis Photodyn Ther. 2023 Jun;42:103504. doi: 10.1016/j.pdpdt.2023.103504. Epub 2023 Mar 11.
BACKGROUND
Photodynamic therapy is an alternative anticancer treatment approach that promises high therapeutic efficacy. In this study, it is aimed to investigate the PDT-mediated anticancer effects of newly synthesized silicon phthalocyanine (SiPc) molecules on MDA-MB-231, MCF-7 breast cancer cell lines, and non-tumorigenic MCF-10A breast cell line.
METHODS
Novel bromo substituted Schiff base (3a), its nitro homolog (3b), and their silicon complexes (SiPc-5a and SiPc-5b) were synthesized. Their proposed structures were confirmed by FT-IR, NMR, UV-vis and MS instrumental techniques. MDA-MB-231, MCF-7 and MCF-10A cells were illuminated at a light wavelength of 680 nm for 10 min, giving a total irradiation dose of 10 j/cm. MTT assay was used to determine the cytotoxic effects of SiPc-5a and SiPc-5b. Apoptotic cell death was analyzed using flow cytometry. Changes in the mitochondrial membrane potential were determined by TMRE staining. Intracellular ROS generation was observed microscopically using HDCFDA dye. Colony formation assay and in vitro scratch assay were performed to analyze the clonogenic activity and cell motility. Transwell migration and matrigel invasion analyzes were conducted to observe changes in the migration and invasion status of the cells.
RESULTS
The combination of SiPc-5a and SiPc-5b with PDT exhibited cytotoxic effects on cancer cells and triggered cell death. SiPc-5a/PDT and SiPc-5b/PDT decreased mitochondrial membrane potential and increased intracellular ROS production. Statistically significant changes were detected in cancer cells' colony-forming ability and motility. SiPc-5a/PDT and SiPc-5b/PDT reduced cancer cells' migration and invasion capacities.
CONCLUSION
The present study identifies PDT-mediated antiproliferative, apoptotic, and anti-migratory characteristics of novel SiPc molecules. The outcomes of this study emphasize the anticancer properties of these molecules and suggest that they may be evaluated as drug-candidate molecules for therapeutic purposes.
背景
光动力疗法是一种有前途的抗肿瘤治疗方法，具有很高的治疗效果。本研究旨在探讨新合成的硅酞菁（SiPc）分子通过光动力疗法对 MDA-MB-231、MCF-7 乳腺癌细胞系和非致瘤性 MCF-10A 乳腺细胞系的抗肿瘤作用。
方法
合成了新型溴取代席夫碱（3a）、其硝基类似物（3b）及其硅配合物（SiPc-5a 和 SiPc-5b）。通过 FT-IR、NMR、UV-vis 和 MS 等仪器技术证实了它们的结构。用波长为 680nm 的光照射 MDA-MB-231、MCF-7 和 MCF-10A 细胞 10 分钟，总辐照剂量为 10j/cm。MTT 法测定 SiPc-5a 和 SiPc-5b 的细胞毒性作用。用流式细胞术分析细胞凋亡。通过 TMRE 染色测定线粒体膜电位的变化。用 HDCFDA 染料观察细胞内 ROS 的产生。用克隆形成实验和体外划痕实验分析细胞的克隆形成活性和细胞迁移能力。Transwell 迁移和 Matrigel 侵袭实验观察细胞迁移和侵袭状态的变化。
结果
SiPc-5a 和 SiPc-5b 与 PDT 联合对癌细胞表现出细胞毒性作用，并触发细胞死亡。SiPc-5a/PDT 和 SiPc-5b/PDT 降低线粒体膜电位，增加细胞内 ROS 产生。癌细胞的集落形成能力和运动能力发生了统计学意义上的显著变化。SiPc-5a/PDT 和 SiPc-5b/PDT 降低了癌细胞的迁移和侵袭能力。
结论
本研究确定了新型 SiPc 分子通过光动力疗法的增殖抑制、凋亡和抗迁移特性。本研究的结果强调了这些分子的抗癌特性，并表明它们可能被评估为治疗目的的候选药物分子。
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