Anti-metastatic and pro-apoptotic effects elicited by combination photodynamic therapy with sonodynamic therapy on breast cancer both in vitro and in vivo |
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| Affiliation: | 1. Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, China;2. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China;3. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China;1. Department of Anatomy, Basic Medical Science College, Harbin Medical University, Harbin, China;2. Laboratory of Sono- and Photo-theranostic Technologies, Harbin Institute of Technology, Harbin, China;3. Department of Oral Pathology, Stomatological Hospital, Harbin Medical University, Harbin, P. R. China;4. Materials Research Institute, The Pennsylvania State University, University Park, PA, USA;1. Department of Veterinary Clinical Medicine, School of Veterinary Medicine, Tottori University, Tottori, Japan;2. Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima, Tokushima, Japan;3. SBI Pharmaceuticals Co., Ltd., Tokyo, Japan;4. ITO Physiotherapy & Rehabilitation, Tokyo, Japan;1. Division of Surgery and Interventional Sci., University College London, Royal Free Hospital, Pond St., London NW3 2PF, UK;2. Biomedical Sciences Research Institute, University of Ulster, Cromore Rd., Coleraine, Co. Derry BT52 1SA, UK;1. College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350116, China;2. Department of Biomedical Engineering and Environmental Science, National Tsing Hua University, Hsinchu 30013, Taiwan |
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| Abstract: | Sono-Photodynamic therapy (SPDT), a new modality for cancer treatment, is aimed at enhancing anticancer effects by the combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT). In this study, we investigated the antitumor effect and possible mechanisms of Chlorin e6 (Ce6) mediated SPDT (Ce6-SPDT) on breast cancer both in vitro and in vivo. MTT assay revealed that the combined therapy markedly enhanced cell viability loss of breast cancer cell lines (MDA-MB-231, MCF-7 and 4T1) compared with SDT and PDT alone. Propidium iodide/hoechst33342 double staining reflected that 4T1 cells with apoptotic morphological characteristics were significantly increased in groups given combined therapy. Besides, the combined therapy caused obvious mitochondrial membrane potential (MMP) loss at early 1 h post SPDT treatment. The generation of intracellular reactive oxygen species (ROS) detected by flow cytometry was greatly increased in 4T1 cells treated with the combination therapy, and the loss of cell viability and MMP could be effectively rescued by pre-treatment with the ROS scavenger N-acetylcysteine (NAC). Further, Ce6-SPDT markedly inhibited the tumor growth (volume and weight) and lung metastasis in 4T1 tumor-bearing mice, but had no effect on the body weight. Hematoxylin and eosin staining revealed obvious tissue destruction with large spaces in the Ce6-SPDT groups, and TUNEL staining indicated tumor cell apoptosis after treatment. Immunohistochemistry analysis showed that the expression level of VEGF and MMP were significantly decreased in the combined groups. These results indicated that Ce6-mediated SPDT enhanced the antitumor efficacy on 4T1 cells compared with SDT and PDT alone, loss of MMP and generation of ROS might be involved. In addition, Ce6-mediated SPDT significantly inhibited tumor growth and metastasis in mouse breast cancer 4T1 xenograft model, in which MMP-9 and VEGF may play a crucial role. |
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| Keywords: | Photodynamic therapy Sonodynamic therapy Chlorin e6 Antitumor Apoptosis Metastasis |
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