Chongjun Shi1, Nini Zhang2, Yang Feng3, Jiewei Cao4, Xuyi Chen5, Bin Liu3,4. 1. Department of Urology, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou, China. 2. The First Women and Children's Hospital of Huizhou, Huizhou, China. 3. The Second Hospital of Hebei Medical University, Shijiazhuang, China. 4. Hebei Medical University, Shijiazhuang, China. 5. Affiliated Hospital of Logistics University of Chinese People's Army Police, Tianjin, China.
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.
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 humanprostate 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.
Authors: Konrad H Stopsack; Ericka M Ebot; Mary K Downer; Travis A Gerke; Jennifer R Rider; Philip W Kantoff; Lorelei A Mucci Journal: Cancer Causes Control Date: 2018-06-18 Impact factor: 2.506
Authors: Ian S Miller; Sonja Khan; Liam P Shiels; Sudipto Das; Alice C O' Farrell; Kate Connor; Adam Lafferty; Bruce Moran; Claudio Isella; Paul Loadman; Emer Conroy; Susan Cohrs; Roger Schibli; Robert S Kerbel; William M Gallagher; Elisabetta Marangoni; Kathleen Bennett; Darran P O' Connor; Róisín M Dwyer; Annette T Byrne Journal: Cancer Med Date: 2022-04-17 Impact factor: 4.711