NSAIDs and Cell Proliferation in Colorectal Cancer 英文参考文献.docVIP

Pharmaceuticals 2010, 3, 2007-2021; doi:10.3390/ph3072007 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review NSAIDs and Cell Proliferation in Colorectal Cancer Raj Ettarh *, Anthony Cullen and Alvise Calamai School of Medicine Medical Science, University College Dublin, C206 Health Sciences Building, Belfield, Dublin 4, Ireland; E-Mails: Anthony.Cullen1@ucdconnect.ie (A.C.); alvise.calamai@ (A.C.) * Author to whom correspondence should be addressed; E-mail: r.ettarh@ucd.ie (R.E.); Tel.: +353-1-716-6631; Fax: +353-1-716-6649 Received: 8 April 2010; in revised form: 17 May 2010 / Accepted: 22 June 2010 / Published: 24 June 2010 Abstract: Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administrat