Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.
O'Byrne, Kenneth J
Pidgeon, Graham P
AffiliationDepartment of Surgery, Institute of Molecular Medicine, Trinity Health Sciences Centre, St. James's Hospital, Dublin 8, Ireland.
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Reverse Transcriptase Polymerase Chain Reaction
Tissue Array Analysis
MetadataShow full item record
CitationExamination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer. 2011, 10:25 Mol. Cancer
AbstractThromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease.
TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression.
TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis.
TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.
- Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer.
- Authors: Cathcart MC, Gately K, Cummins R, Drakeford C, Kay EW, O'Byrne KJ, Pidgeon GP
- Issue date: 2014 May
- Differential expression of thromboxane synthase in prostate carcinoma: role in tumor cell motility.
- Authors: Nie D, Che M, Zacharek A, Qiao Y, Li L, Li X, Lamberti M, Tang K, Cai Y, Guo Y, Grignon D, Honn KV
- Issue date: 2004 Feb
- Prostacyclin synthase expression and epigenetic regulation in nonsmall cell lung cancer.
- Authors: Cathcart MC, Gray SG, Baird AM, Boyle E, Gately K, Kay E, Cummins R, Pidgeon GP, O'Byrne KJ
- Issue date: 2011 Nov 15
- Methionine Aminopeptidase 2 as a Potential Therapeutic Target for Human Non-Small-Cell Lung Cancers.
- Authors: Shimizu H, Yamagishi S, Chiba H, Ghazizadeh M
- Issue date: 2016 Jan-Feb
- Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27.
- Authors: Leung KC, Hsin MK, Chan JS, Yip JH, Li M, Leung BC, Mok TS, Warner TD, Underwood MJ, Chen GG
- Issue date: 2009 Oct 15