Sinoporphyrin sodium is a promising sensitizer for photodynamic and sonodynamic therapy in glioma

Abstract

The aim of the present study was to explore the antitumor effects of sinoporphyrin sodium (DVDMS)-mediated photodynamic therapy (PDT) and sonodynamic therapy (SDT) in glioma, and to reveal the underlying mechanisms. The uptake of DVDMS by U-118 MG cells was detected by flow cytometry (FCM). A 630-nm semiconductor laser and 1-MHz ultrasound were used to perform PDT and SDT, respectively. Cell proliferation and apoptosis were evaluated using the Cell Counting Kit-8 assay, FCM and Hoechst 33258 staining, respectively. Western blot analysis was used to detect protein expression and phosphorylation levels. BALB/c nude mice were used to establish a xenograft model of U-118 MG cells. DVDMS was injected intravenously and PDT and SDT were performed 24 h later. An in vivo imaging system was used to evaluate the fluorescence of DVDMS, to measure tumor sizes, and to evaluate the therapeutic effects. The uptake of DVDMS by U-118 MG cells was optimal after 4 h. PDT and SDT following DVDMS injection significantly inhibited the proliferation and increased apoptosis of glioma cells in vitro (P<0.05, P<0.01) respectively. In vivo, the fluorescence intensity of DVDMS was lower in the PDT and SDT groups compared with the DVDMS group, while tumor cell proliferation and weight were lower in the PDT and SDT groups than in the control group (P<0.05, P<0.01). However, there was no significant difference when laser, ultrasound or DVDMS were applied individually, compared with the control group. Hematoxylin and eosin staining suggested that both PDT and SDT induced significant apoptosis and vascular obstruction in cancer tissues. DVDMS-mediated PDT and SDT inhibited the expression levels of proliferating cell nuclear antigen (PCNA) and Bcl-xL, increased cleaved-caspase 3 levels, and decreased the protein phosphorylation of the PI3K/AKT/mTOR signaling pathway. Changes in the expression of PCNA, and Bcl-xL and in the levels of cleaved-caspase 3 were partly reversed by N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger. Similar results were obtained with FCM. DVDMS-mediated PDT and SDT inhibited glioma cell proliferation and induced cell apoptosis in vitro and in vivo, potentially by increasing the generation of ROS and affecting protein expression and phosphorylation levels.

Research progress of berberine mediated photodynamic therapy (Review)

“…SDT is a promising new option for the invasive treatment of tumors ( 62 ). SDT is similar to PDT in that it requires the combination of sensitizers, ultrasound and molecular oxygen ( 61 ).…”

Sonodynamic Therapy for the Treatment of Intracranial Gliomas

“…Overall, four studies in vitro observed a selective accumulation of DVDMS compounds in glioma cells, which was generally superior in liposomal compounds than for the dye alone [ 71 , 72 , 73 , 74 ]. All studies reported higher rates of apoptosis, necrosis and growth inhibition in SDT schemes; sonication alone was inferior to sonodynamic therapy.…”

“…All studies reported higher rates of apoptosis, necrosis and growth inhibition in SDT schemes; sonication alone was inferior to sonodynamic therapy. In vivo models, employing either subcutaneous grafts [ 71 , 73 , 74 ] or intracerebral inoculation [ 72 ] of glioma cells, highlighted that SDT granted a significant survival benefit in treated groups compared to both controls and subjects who were only sonicated. Moreover, histopathological analyses observed elevation of apoptosis markers; in particular, Wen An et al reported that both SDT and PDT reduced Bcl-x and p62 expression [ 74 ].…”

“…In vivo models, employing either subcutaneous grafts [ 71 , 73 , 74 ] or intracerebral inoculation [ 72 ] of glioma cells, highlighted that SDT granted a significant survival benefit in treated groups compared to both controls and subjects who were only sonicated. Moreover, histopathological analyses observed elevation of apoptosis markers; in particular, Wen An et al reported that both SDT and PDT reduced Bcl-x and p62 expression [ 74 ]. Interestingly, this study also found that fluorescence of the subcutaneous grafts decreased after both SDT and PDT, suggesting a photobleaching effect of both treatments, which would corroborate the sonoluminescence theory [ 74 ].…”

“…Moreover, histopathological analyses observed elevation of apoptosis markers; in particular, Wen An et al reported that both SDT and PDT reduced Bcl-x and p62 expression [ 74 ]. Interestingly, this study also found that fluorescence of the subcutaneous grafts decreased after both SDT and PDT, suggesting a photobleaching effect of both treatments, which would corroborate the sonoluminescence theory [ 74 ]. Only Pi et al have employed a cerebral glioma model, which allowed them to observe far more significant survival increase and apoptosis markers in subjects also undergoing US-mediated disruption of the BBB [ 72 ].…”