Journal Article


Martin Clynes
Annemarie Larkin
Lisa Connolly
Mary Heenan
Robert O'Connor



drug effects antagonists inhibitors mice nude drug therapy cell line tumor carcinoma large cell antineoplastic combined chemotherapy protocols biosynthesis cell division mice pathology doxorubicin p glycoprotein administration dosage humans metabolism lung neoplasms xenograft model antitumor assays pharmacology animals drug synergism female sulindac

Increased anti-tumour efficacy of doxorubicin when combined with sulindac in a xenograft model of an MRP-1-positive human lung cancer. (2004)

Abstract A number of cellular proteins, including P-glycoprotein (P-gp) and Multiple drug Resistance Protein (MRP-1), act as drug efflux pumps and are important in the resistance of many cancers to chemotherapy. We previously reported that a small number of NSAIDs could inhibit the activity of MRP-1. We chose sulindac as a candidate agent for further investigation as it has the most favourable efficacy and toxicity profile of the agents available for a potential specific MRP-1 inhibitor. NCI H460 cells expressed MRP-1 protein (by Western blot) and also the toxicity of doxorubicin (a substrate of MRP-1) could be potentiated in this line using non-toxic concentrations of the MRP-1 substrate/inhibitor sulindac. These cells were implanted in nude mice and the animals divided into various groups which were administered doxorubicin and/or sulindac. Sulindac was shown to significantly potentiate the tumour growth inhibitor activity of doxorubicin in this MRP-1-overexpressing human tumour xenograft model. Sulindac may be clinically useful as an inhibitor of the MRP-1 cancer resistance mechanism.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Martin Clynes, Annemarie Larkin, Lisa Connolly, Mary Heenan, Robert O'Connor

Experts in our system

Martin Clynes
Dublin City University
Total Publications: 232
Annemarie Larkin
Dublin City University
Total Publications: 26
Robert O'Connor
Dublin City University
Total Publications: 74