2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Flurbiprofen suppresses the inflammation, proliferation, invasion and migration of colorectal cancer cells via COX2

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Colorectal cancer is an aggressive disease with a poor prognosis and low survival rate at the advanced stage, therefore new innovative targets are urgently required. Flurbiprofen has been reported to exhibit therapeutic effects in other types of cancer, such as esophageal cancer, breast cancer and colorectal cancer. Therefore, the present study aimed to investigate the function of flurbiprofen in colorectal cancer. SW620 colorectal cancer cells were treated with different concentrations of flurbiprofen to determine the optimum concentration. Subsequently, COX2 expression affected by flurbiprofen was tested using western blotting, reverse transcription-quantitative PCR and immunofluorescence. Enzyme-linked immunosorbent assay was used to determine the levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β. Cell Counting Kit-8, colony formation and flow cytometry assays were used to assess the proliferation and apoptosis of SW620 cells in various groups. Western blotting was performed to investigate the expression of proliferation-, apoptosis- and migration-related proteins after different treatments. Wound healing and Transwell assays were performed to measure the invasion and migration of colorectal cancer cells, respectively. The results demonstrated that flurbiprofen inhibited colorectal cancer cell proliferation. Furthermore, it was identified that flurbiprofen inhibited the expression of COX2. Notably, flurbiprofen suppressed the expression of inflammatory factors by inhibiting COX2. Moreover, flurbiprofen inhibited the proliferation, invasion and migration of colorectal cancer cells by inhibiting COX2. In conclusion, the present study revealed that flurbiprofen inhibited COX2 expression in colorectal cancer, and affected the proliferation, invasion, migration and apoptosis of colorectal cancer cells. These results expand the understanding of the function of COX2 in colorectal cancer and the effect of flurbiprofen on COX2 expression.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Diagnostic Potential and Interactive Dynamics of the Colorectal Cancer Virome

          Colorectal cancer is a leading cause of cancer-related death in the United States and worldwide. Its risk and severity have been linked to colonic bacterial community composition. Although human-specific viruses have been linked to other cancers and diseases, little is known about colorectal cancer virus communities. We addressed this knowledge gap by identifying differences in colonic virus communities in the stool of colorectal cancer patients and how they compared to bacterial community differences. The results suggested an indirect role for the virome in impacting colorectal cancer by modulating the associated bacterial community. These findings both support the idea of a biological role for viruses in colorectal cancer and provide a new understanding of basic colorectal cancer etiology.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            KRAS Mutation and Consensus Molecular Subtypes 2 and 3 Are Independently Associated with Reduced Immune Infiltration and Reactivity in Colorectal Cancer

            Purpose KRAS mutation is a common canonical mutation in CRC, found at differing frequencies in all Consensus Molecular Subtypes (CMS). The independent immunobiological impacts of RAS mutation and CMS are unknown. Thus, we explored the immunobiological effects of KRAS mutation across the CMS spectrum. Experimental Design Expression analysis of immune genes/signatures was performed using The Cancer Genome Atlas (TCGA) RNA-seq and the KFSYSCC microarray datasets. Multivariate analysis included KRAS status, CMS, tumour location, MSI status, and neoantigen load. Protein expression of STAT1, HLA-Class II, and CXCL10 was analysed by digital immunohistochemistry. Results The Th1-centric co-ordinate immune response cluster (CIRC) was significantly, albeit modestly, reduced in KRAS mutant CRC in both data sets. Cytotoxic T cells, neutrophils and the interferon gamma pathway were suppressed in KRAS mutant samples. The expression of STAT1 and CXCL10, were reduced at the mRNA and protein levels. In multivariate analysis KRAS mutation, CMS2 and CMS3 were independently predictive of reduced CIRC expression. Immune response was heterogeneous across KRAS mutant CRC: CMS2 KRAS mutant samples have the lowest CIRC expression, reduced expression of the interferon gamma pathway, STAT1 and CXCL10 and reduced infiltration of cytotoxic cells and neutrophils relative to CMS1 and CMS4 and to CMS2 KRAS wild type samples in the TCGA. These trends held in the KFSYSCC data set. Conclusions KRAS mutation is associated with suppressed Th1/cytotoxic immunity in CRC, the extent of the effect being modulated by CMS subtype. These results add a novel immunobiological dimension to the biological heterogeneity of CRC.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction

              We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.
                Bookmark

                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                November 2020
                20 August 2020
                20 August 2020
                : 20
                : 5
                : 132
                Affiliations
                [1 ]Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
                [2 ]Traditional Medicine Center, Jinhua Hospital, Zhejiang University, Jinhua, Zhejiang 321000, P.R. China
                [3 ]Physical Examination Center, Jinhua Hospital, Zhejiang University, Jinhua, Zhejiang 321000, P.R. China
                Author notes
                Correspondence to: Dr Feng Ji, Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, P.R. China, E-mail: 1189005@ 123456zju.edu.cn
                Article
                OL-0-0-11993
                10.3892/ol.2020.11993
                7471702
                0bf13062-8aa2-4269-bb4f-8a33a5832789
                Copyright: © Wang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 17 February 2020
                : 02 July 2020
                Categories
                Articles

                Oncology & Radiotherapy
                flurbiprofen,cyclooxygenase 2,colorectal cancer
                Oncology & Radiotherapy
                flurbiprofen, cyclooxygenase 2, colorectal cancer

                Comments

                Comment on this article