Anti-metastatic and pro-apoptotic effects elicited by combination photodynamic therapy with sonodynamic therapy on breast cancer both in vitro and in vivo

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.

Hypericin-mediated sonodynamic therapy induces autophagy and decreases lipids in THP-1 macrophage by promoting ROS-dependent nuclear translocation of TFEB

“…8 SDT induces the generation of reactive oxygen species (ROS) and apoptosis in tumor cells, and has been shown to greatly improve the outcome of cancer patient by promoting tumor shrinkage while reducing metastases of tumor cells. 9, 10, 11, 12, 13 We previously revealed that SDT could effectively induce apoptosis of macrophage and macrophage foam cell via mitochondrial-caspase dependent pathway 14, 15 and rapidly stabilize atherosclerotic plaques. 16 Meanwhile, SDT possesses high repeatability owing to its relative security and accessibility.…”

Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

“…11,12 Besides, it is currently believed that the combination of PDT and sonodynamic therapy (SDT) may decrease the sensitizer dosage and ultrasound/ light energy, which can further reduce the side effects, while enhancing the curative effect dramatically. [13][14][15][16][17] Thus, PDT combined with SDT (PSDT) is considered for the lesion of deep site in the present study. The underlying mechanisms of PDT and SDT are quite different, and the mechanisms of PSDT are very complicated.…”

“…The effect of PDT and SDT combination therapy is coincident with previous reports, except that in our study, the process was activated in sequence by light and ultrasound. 14,16 The cellular uptake and intracellular distribution of sensitizers is potentially important for PDT and SDT. So, we determined the uptake ability of MH7A cells for free ICG and OI-NPs.…”

“…16 Many morphologic characteristics related to apoptosis, including cell shrinkage, nuclear chromatin condensation, and DNA fragmentation, have been defined clearly. To confirm whether cell apoptosis was induced, flow cytometry and HO/PI double staining were performed in our study.…”

Sonodynamic action of chlorin e6 on Staphylococcus aureus and Escherichia coli

“…The plane transducer was placed in a water tank filled with degassed water and the temperature was kept at 37°C during ultrasonic exposure. The ultrasound parameters were measured as described in our previous studies [17].…”