sinoporphyrin-sodium and Lung-Neoplasms

Sonodynamic therapy (SDT), wherein focused ultrasound is used to guide the site-specific delivery of nano-sonosensitizers and trigger profound sono-damage, has great potential in cancer theranostics. The development of nanosensitizers with high sono-activatable efficiency and good biosafety is however challenging.

Topics: Animals; Biocompatible Materials; Breast Neoplasms; Cell Death; Cell Line; Cell Proliferation; Drug Liberation; Endocytosis; Exosomes; Female; Humans; Hydrogen-Ion Concentration; Lung Neoplasms; Mice, Inbred BALB C; Nanoparticles; Neoplasms; Porphyrins; Singlet Oxygen; Tissue Distribution; Ultrasonic Therapy

Sonodynamic therapy (SDT) is expected to be a new method to solve the clinical problems caused by advanced metastasis in patients with lung cancer. The use of ultrasound has the advantage of being noninvasive, with deep-penetration properties. This study explored the anti-tumor effect of SDT with a new sonosensitizer, sinoporphyrin sodium (DVDMS), on the human small cell lung cancer H446 cell line in vitro and in vivo.. Absorption of DVDMS was detected by a fluorescence spectrophotometer, and DVDMS toxicity was determined using a Cell Counting Kit-8. Mitochondrial membrane potential (MMP) was assessed using the JC-1 fluorescent probe. Cell apoptosis was measured by flow cytometry, and apoptosis-related proteins were detected by western blotting. The expression of cytokines was measured using an enzyme-linked immunosorbent assay and quantitative real-time PCR. To verify the in vitro results, we detected tumor volumes and weight changes in a xenograft nude mouse model after DVDMS-SDT. Hematoxylin and eosin staining was used to observe changes to the tumor, heart, liver, spleen, lung, and kidney of the mice, and immunohistochemistry was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in tumor tissues.. DVDMS-SDT-treated H446 cells increased the rate of cellular apoptosis and the levels of reactive oxygen species (ROS), cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and caspase-10, and decreased the levels of MMP, RIP3, B-cell lymphoma 2, vascular endothelial growth factor, and tumor necrosis factor-α. The sonotoxic effect was mediated by ROS and was reduced by a ROS scavenger (N-acetyl-L-cysteine). In the in vivo mouse xenograft model, DVDMS-SDT showed efficient anti-cancer effects with no visible side effects.. DVDMS-SDT induced apoptosis in H446 cells, in part by targeting mitochondria through the mitochondria-mediated apoptosis signaling pathway, and the extrinsic apoptosis pathway was also shown to be involved. Both apoptosis and changes in RIP3 expression were closely related to the generation of ROS. DVDMS-SDT will be advantageous for the management of small cell lung cancer due to its noninvasive characteristics.

Topics: Animals; Apoptosis; Cell Line, Tumor; Down-Regulation; Female; Humans; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Porphyrins; Receptor-Interacting Protein Serine-Threonine Kinases; Small Cell Lung Carcinoma; Ultrasonic Therapy

Sinoporphyrin sodium (DVDMS) is a newly identified photosensitizer that was isolated from Photofrin. Experimental and clinical results have demonstrated that repeated application of PDT greatly improved the therapeutic efficacy. Here, we comparatively studied two kinds of photodynamic therapy (PDT) strategies by using DVDMS (2mg/kg) in murine breast cancer 4T1 xenograft model to provide evidence which strategy exerts a better antitumor effect. Regimen (1): DVDMS was injected one time into tumor-bearing mice, which were then repeatedly exposed to 50J/cm(2) light 24h, 30h and 36h later. Regimen (2): DVDMS was injected 3 times and mice exposed to 50J/cm(2) light 24h after each injection, with 5days intervals between each DVDMS injection. On day 21 after the tumor cell injection, in regimen (1) the tumor volume inhibition ratio was reached to 85.75±7.60%. While at the same day the inhibition ratio was 65.74±8.64% of regimen (2). Additionally, regimen (1) appeared to more effectively initiate tumor tissue destruction and cancer cell apoptosis, inhibit lung metastasis, suppress cancer cell proliferation and angiogenesis. Moreover, no obvious effect on body weight and other side effects were observed in the treated mice. These results suggest that regimen (1) might be a potentially efficient strategy against breast cancer.

Topics: Animals; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Immunohistochemistry; Light; Lung Neoplasms; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Neovascularization, Pathologic; Photochemotherapy; Photosensitizing Agents; Porphyrins; Transplantation, Homologous