Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer

Molecular Cancer

Research

Kenneth J O'Byrne¹  Kathy Gately¹  Elaine Kay²  Robert Cummins²  Graham P Pidgeon³  Mary-Clare Cathcart³ 

[1] Department of Clinical Medicine, Institute of Molecular Medicine, Trinity Health Sciences Centre, St. James's Hospital, Dublin 8, Ireland;Department of Pathology, Beaumont Hospital, Dublin 9, Ireland;Department of Surgery, Institute of Molecular Medicine, Trinity Health Sciences Centre, St. James’s Hospital, Dublin 8, Ireland;

关键词: NSCLC Cell Line;    NSCLC Tissue;    High Content Screening;    Foetal Bovine Serum Medium;    Cell Death Detection ELISA;   

DOI  :  10.1186/1476-4598-10-25

 received in 2010-11-16, accepted in 2011-03-09,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThromboxane 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.MethodsTXS 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.ResultsTXS 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.ConclusionTXS 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.

【 授权许可】

Unknown   
© Cathcart et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.