['Induction of apoptosis by the death ligand TRAIL might be a promising therapeutic approach in colorectal cancer therapy. However, some colon cancer cells are resistant to TRAIL because of the expression of anti-apoptotic proteins, such as FLIP. We studied the role of FLIP for apoptosis resistance in colon cancer and developed an approach to overcome the resistance to TRAIL.', 'The mechanisms of TRAIL-induced cell death in colon cancer cells were studied by Western blot analysis, apoptosis assays, transient and stable transfections, siRNA-mediated knockdown, and FACS analysis.', 'The anti-apoptotic protein FLIP is expressed in the majority of colon carcinoma. Stable over-expression of FLIP renders colon carcinoma cells resistant to the death ligand, TRAIL. siRNA-mediated down-regulation of FLIP sensitizes the cells to TRAIL-induced apoptosis. FLIP-expressing colon cancer cells can be sensitized to TRAIL-induced apoptosis by the anti-diabetic drug troglitazone. Troglitazone induces a pronounced reduction in protein expression levels of FLIP. The troglitazone-dependent down-regulation of FLIP occurs on a post-translational level and involves the accelerated FLIP degradation by the proteasome. Moreover, troglitazone suppresses the expression of the anti-apoptotic protein, survivin, and induces the cell surface expression of the TRAIL receptor 2.'] Does [ The anti-diabetic drug troglitazone sensitize colon cancer cells to TRAIL-induced apoptosis by down-regulating FLIP ]?