MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS

Abstract

BackgroundBreast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells.MethodsUptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining.ResultsFollowing MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced the expression of F-actin in cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo.ConclusionTaken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis.

Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol

“…Excessive ROS production has been shown to associate with cisplatin-induced cell death. To demonstrate ROS reducing and anti-oxidation ability of HNK, membrane permeable 2′,7′-dichlorofluorescein diacetate (DCFH-DA), a compound that can actively reacts with multiple ROS species [ 37 ] was used. We showed an increased cytotoxicity of cisplatin when concentration was ≥15 μM; however, this was not observed for HNK up to 25 μM ( Figure S1 ).…”

Photodynamic therapy induces autophagy-mediated cell death in human colorectal cancer cells via activation of the ROS/JNK signaling pathway

“…Evidence has shown that a PS is activated via light exposure to produce ROS and induce oxidative stress. PS-mediated PDT further induces cell apoptosis and autophagy in cancer cells 31 , 43 , 44 . In this study, flow cytometry assays indicated that m-THPC-PDT markedly induced the apoptosis of CRC cells.…”

Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism

“…Human MMP-9 gene is located on chromosome 20q13.12 [ 33 ]. Related studies have shown that [ 34 , 35 ] MMP-9 overexpression is closely related to tumor invasion and migration. In our study, with Hon intervention, the invasion and migration of HER2-positive gastric cancer cells were significantly inhibited, and MMP-9 protein and mRNA expression were also significantly inhibited.…”