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Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.
Cathcart, Mary-Clare; Gately, Kathy; Cummins, Robert; Kay, Elaine W; O'Byrne, Kenneth J; Pidgeon, Graham P
<p>This article is also available from <a href=""></a></p> <p>BACKGROUND: Thromboxane 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.</p> <p>METHODS: 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.</p> <p>RESULTS: 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.</p> <p>CONCLUSION: 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.</p>
Keyword(s): Adenocarcinoma; Apoptosis; Blotting; Western; Carcinoma; Non-Small-Cell Lung; Cell Line; Tumor; Cell Proliferation; Cyclooxygenase 2; Enzyme Inhibitors; Female; Gene Expression Regulation; Enzymologic; Neoplastic; Humans; Immunohistochemistry; Lung Neoplasms; Male; Prognosis
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Type: Journal article
Peer-Reviewed: Yes
Institution: Royal College of Surgeons in Ireland
Citation(s): Cathcart MC, Gately K, Cummins R, Kay E, O'Byrne KJ, Pidgeon GP. Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer. Molecular Cancer. 2011;10:25.
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First Indexed: 2015-07-31 15:36:29 Last Updated: 2018-02-13 07:18:39