The efficacy of SB on HT-29 cells was in a dose- and time-dependent manner with the LD50 achieved at 550 µg/mL and 72-hour incubation. A 50% reduction in size of the excised tumors was determined in SB-treated xenografts (10 mg/kg/day)

for 21 days when compared with that of the untreated control tumors. For the hTERT mRNA expression, a 1.3-fold down-regulation was quantitated in HT-29 cells at LD50; whereas a 0.6-fold reduction was quantitated in selleck kinase inhibitor SB-treated excised tumors at Day 21. In summary, SB was effective not only to inhibit HT-29 colon cells, but also reduce the tumor size of the colon cancer xenografts. The hTERT mRNA expression was down-regulated by SB in both in vitro and in vivo models. Thus, hTERT could be an effective marker for monitoring SB treatment for colon cancer. This study is supported by the Central Research Grant of The Hong Kong Polytechnic University (G-YG88). Poster No. 38 Evidence for a Role of MAGI1 in Colon Carcinoma Invasion Jelena Zaric 1 , Curzio Ruegg1,2 1 Division of Experimental Oncology, Centre Pluridisciplinaire d’Oncologie, Lausanne University Hospital,

University of Lausanne, Epalinges, Switzerland, 2 National Center for Competence in Research, Molecular Oncology, ISREC-EPFL, Lausanne, Switzerland Colorectal cancer (CRC) is the second most common type of malignancy in the Western world. COX-2 derived PGE2 promotes CRC progression. However, increased cardiovascular risks of selective COX-2 inhibitors limit their use in chemoprevention. We have observed that Celebrex induces a scaffolding protein MAGI1 (Membrane Associated AZD0156 order Guanylate Kinase with Inverted domain structure -1) in COX-2 positive colon carcinoma-derived cell lines (e.g. SW480, HCT116, HT29). MAGI1 appears to function as scaffold that assemble multimolecular complexes at functionally relevant subcellular sites in polarized epithelial cells. When overexpressed, this inner membrane 5-FU chemical structure associated protein completely inhibited both migration and invasion of colon carcinoma cells in vitro. Moreover, MAGI1 enabled colon cancer cells

to re-establish cell-to-cell contacts leading to epithelial-like phenotype and increased adhesion on different extracellular matrix proteins. Conversely, stable MAGI1 knock-down though an shRNA approach, favored anchorage independent cell growth. One of the reported MAGI1 binding partners in cell junction complexes is beta-catenin. MAGI1 overexpression induced increased beta-catenin membrane localization while its activity as transcription factor was decreased. The opposite effects were observed in cells in which MAGI1 was knock-down. We are currently testing the effect of of MAGI1 modulation in tumour growth, local invasion and distant metastasis formation. The screening for MAGI1 expression in colon carcinoma tissue is also in progress.