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Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Shi, Chongjun Zhang, Nini Feng, Yang Cao, Jiewei Chen, Xuyi Liu, Bin |
| Copyright Year | 2017 |
| Abstract | BACKGROUND/AIMS Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. METHODS Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB) kinase-β (IKK-β) phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. RESULTS We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB) activation, inhibitor of κB (IκB)-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK)- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. CONCLUSION The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of metastatic prostate cancer. |
| Starting Page | 1313 |
| Ending Page | 1324 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.karger.com/Article/Pdf/464434 |
| PubMed reference number | 28278500v1 |
| Alternate Webpage(s) | https://doi.org/10.1159/000464434 |
| DOI | 10.1159/000464434 |
| Journal | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology |
| Volume Number | 41 |
| Issue Number | 4 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Aspirin Basement membrane Cell Invasion Cell Nucleus Contribution Extracellular Matrix Gelatin Malignant neoplasm of prostate Matrix Metalloproteinase 9 Matrix Metalloproteinases Metalloproteases Peptide Hydrolases Plasminogen Activator Prostate carcinoma Prostatic Neoplasms SERPINE1 protein, human Serine Proteases Urokinase alteplase cancer cell kinase activity |
| Content Type | Text |
| Resource Type | Article |
