Silva Camila Ramos, Vieira Daniel Perez, de Freitas Anderson Zanardi, Ribeiro Martha Simões
Center for Lasers and Applications, Energy and Nuclear Research Institute (IPEN-CNEN), Av. Lineu Prestes, 2242, São Paulo, Brazil.
Center of Biotechnology, Energy and Nuclear Research Institute (IPEN-CNEN), Av. Lineu Prestes, 2242, São Paulo, Brazil.
Breast Cancer Res Treat. 2025 Apr;210(3):687-697. doi: 10.1007/s10549-024-07607-0. Epub 2025 Jan 8.
Triple-negative breast cancer (TNBC) accounts for 20% of all breast cancer cases and is notably resistant to radiotherapy (RT). Photodynamic therapy (PDT) using porphyrins or their derivatives has shown promise as a potential cancer treatment and immune activator. This study evaluated the effects of combining PDT and RT in sublethal conditions for TNBC using in vitro and in vivo models.
In vitro, PDT was combined with RT (2.5 Gy) using a porphyrin (TMPyP, 32 μmolL) and red light (660 ± 15 nm) with a dose of 50 Jcm. We assessed cell viability, survival, apoptosis, ROS, singlet oxygen, and GSH/GSSG ratio. In vivo, we used a TNBC-bearing mouse model and combined PDT with RT in four sessions, comparing treatment sequences. We evaluated tumor volume, clinical manifestations, survival, metastasis in the lungs, ROS, singlet oxygen, and glutathione levels.
Cells treated with PDT + RT had a lower survival fraction, although PDT alone showed higher apoptosis and singlet oxygen levels than RT-treated groups. In vivo, the treatment sequence plays a crucial role: PDT after RT resulted in better clinical outcomes, prolonged survival, and fewer lung nodules compared to RT, with higher singlet oxygen levels likely stimulating an immune response.
Our results show that PDT can be a valuable adjunct in the RT of TNBC, with the treatment sequence playing a crucial role in enhancing efficacy.
三阴性乳腺癌（TNBC）占所有乳腺癌病例的20%，且对放射治疗（RT）具有显著抗性。使用卟啉或其衍生物的光动力疗法（PDT）已显示出作为一种潜在的癌症治疗和免疫激活剂的前景。本研究使用体外和体内模型评估了在亚致死条件下将PDT与RT联合用于TNBC的效果。
在体外，使用卟啉（四甲基吡啶基卟啉，32 μmol/L）和红光（660 ± 15 nm），剂量为50 J/cm²，将PDT与RT（2.5 Gy）联合使用。我们评估了细胞活力、存活率、细胞凋亡、活性氧（ROS）、单线态氧以及谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）比值。在体内，我们使用了携带TNBC的小鼠模型，并将PDT与RT分四个疗程联合使用，比较治疗顺序。我们评估了肿瘤体积、临床表现、存活率、肺转移、ROS、单线态氧和谷胱甘肽水平。
接受PDT + RT治疗的细胞存活率较低，尽管单独使用PDT时细胞凋亡和单线态氧水平高于接受RT治疗的组。在体内，治疗顺序起着关键作用：与RT相比，先进行RT后进行PDT可产生更好的临床效果、延长生存期并减少肺结节，较高的单线态氧水平可能刺激免疫反应。
我们的结果表明，PDT可以成为TNBC放疗中有价值的辅助手段，治疗顺序在提高疗效方面起着关键作用。
