Department of Biophysics, Institute of Physics, Faculty of Science, P.J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia.
Center for Interdisciplinary Biosciences, Technology and Innovation Park, P.J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia.
J Photochem Photobiol B. 2022 Sep;234:112539. doi: 10.1016/j.jphotobiol.2022.112539. Epub 2022 Aug 8.
Nowadays, photobiomodulation (PBM) in combination with chemotherapy or other therapeutic approaches is an attractive adjuvant modality for cancer treatment. Targeted destruction of cancer cells is one of the main advantages of photodynamic therapy (PDT). We have shown in previous studies that the combination of PBM at 808 nm and hypericin-mediated PDT increases PDT efficacy in human glioblastoma cells U87 MG. The study presented here shows significant differences between U87 MG and non-cancerous human dermal fibroblasts (HDF) cells treated by PBM and PDT. This study focuses on mitochondria because PBM mainly affects these organelles. We demonstrated that an interplay between mitochondrial and autophagic proteins plays a crucial role in the response of HDF cells to PBM and PDT. Fluorescence microscopy, flow cytometry, and Western blot analysis were used to examine the autophagic profile of HDF cells after these treatments. An increase in ubiquitin, SQSTM1, LC3BII, and cytochrome c was accompanied by a decrease in M6PR, ATG16L1, and Opa1 in HDF cells exposed to PBM and PDT. Overall, we observed that the switching of autophagy and apoptosis is dose-dependent and also occurs independently of PBM in HDF cells after hypericin-mediated PDT. However, PBM might preferentially induce autophagy in noncancer cells, which might escape apoptosis under certain conditions.
如今，光生物调节（PBM）与化疗或其他治疗方法相结合，是癌症治疗的一种有吸引力的辅助方式。光动力疗法（PDT）的主要优势之一是靶向破坏癌细胞。我们之前的研究表明，808nm 的 PBM 与金丝桃素介导的 PDT 联合使用可提高人胶质母细胞瘤 U87 MG 细胞的 PDT 疗效。本研究显示了经 PBM 和 PDT 处理的 U87 MG 和非癌细胞人真皮成纤维细胞（HDF）之间的显著差异。该研究主要关注线粒体，因为 PBM 主要影响这些细胞器。我们证明了线粒体和自噬蛋白之间的相互作用在 HDF 细胞对 PBM 和 PDT 的反应中起着至关重要的作用。荧光显微镜、流式细胞术和 Western blot 分析用于检查这些处理后 HDF 细胞的自噬谱。在 HDF 细胞中，暴露于 PBM 和 PDT 后，泛素、SQSTM1、LC3BII 和细胞色素 c 的增加伴随着 M6PR、ATG16L1 和 Opa1 的减少。总的来说，我们观察到自噬和细胞凋亡的转换是剂量依赖性的，并且在 HDF 细胞中也独立于金丝桃素介导的 PDT 发生。然而，PBM 可能优先诱导非癌细胞中的自噬，在某些条件下，这些细胞可能逃避细胞凋亡。
