MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS
| Autor: | Qing Chen, Hai-Dan Lin, Dingqun Bai, Liyi Huang, Lehua Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research MMP2 Photodynamic therapy Metastasis chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine Invasion Cell Movement LY294002 Neoplasm Metastasis Phosphorylation Migration Photosensitizing Agents Matrigel Invasion Assay lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gene Expression Regulation Neoplastic Oncology Matrix Metalloproteinase 9 030220 oncology & carcinogenesis MCF-7 Cells Female Research Article Signal Transduction Porphyrins Cell Survival Breast tumor Mice Nude Breast Neoplasms lcsh:RC254-282 03 medical and health sciences Breast cancer Genetics medicine Animals Humans Neoplasm Invasiveness Viability assay Protein kinase B PI3K/AKT/mTOR pathway Transcription Factor RelA medicine.disease Xenograft Model Antitumor Assays Actins 030104 developmental biology chemistry Photochemotherapy Cancer research Reactive Oxygen Species Proto-Oncogene Proteins c-akt |
| Zdroj: | BMC Cancer BMC Cancer, Vol 19, Iss 1, Pp 1-11 (2019) |
| ISSN: | 1471-2407 |
| Popis: | Background Breast 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. Methods Uptake 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. Results Following 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. Conclusion Taken 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink