ABSTRACT
BACKGROUND: Colorectal cancer is the third most common cancer in the western world. Chemotherapy is often ineffective to treat the advanced colorectal cancers due to the chemo-resistance. A major contributor to chemo-resistance is tumour-derived inhibition or avoidance of apoptosis. Insulin-like growth factor I (IGF-I) has been known to play a prominent role in colorectal cancer development and progression. The role of IGF-I in cancer cell apoptosis is not completely understood. METHODS: Using three colorectal cancer cell lines and one muscle cell line, associations between IGF-I and activities of caspase 3/7, 8 and 9 have been examined; the role of insulin-like growth factor I receptor (IGF-IR) in the caspase activation has been investigated. RESULTS: The results show that exogenous IGF-I significantly increases activity of caspases 3/7, 8 and 9 in all cell lines used; blocking IGF-I receptor reduce IGF-I-induced caspase activation. Further studies demonstrate that IGF-I induced caspase activation does not result in cell death. This is the first report to show that while IGF-I activates caspases 3/7, 8 and 9 it does not cause colorectal cancer cell death. CONCLUSION: The study suggests that caspase activation is not synonymous with apoptosis and that activation of caspases may not necessarily induce cell death.
Subject(s)
Apoptosis/drug effects , Caspases/metabolism , Colorectal Neoplasms/enzymology , Insulin-Like Growth Factor I/pharmacology , Cell Growth Processes/drug effects , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Enzyme Activation/drug effects , HCT116 Cells , HT29 Cells , Humans , Isoenzymes , Muscle, Skeletal/drug effects , Muscle, Skeletal/enzymology , Receptor, IGF Type 1/metabolismABSTRACT
There is a critical clinical need for small-diameter bypass grafts, with applications involved in the coronary artery and lower limb. Commercially available materials give rise to unfavorable responses when in contact with blood and subjected to low-flow hemodynamics and, thus, are nonideal as small-diameter bypass grafts. Optimizing the mechanical properties to match both the native artery and the graft surfaces has received keen attention. Endothelialization of bypass grafts is considered a protective mechanism where the biochemicals produced from endothelial cells exert a range of favorable responses, including antithrombotic, noninflammatory responses and inhibition of intimal hyperplasia. In situ endothelialization is most desirable. Nanotechnology approaches facilitate all aspects of endothelialization, including endothelial progenitor cell mobilization, migration, adhesion, proliferation and differentiation. 'Surface nanoarchitecturing mechanisms', which mimic the natural extracellular matrix to optimize endothelial progenitor cell interaction and controlled delivery of various factors in the form of nanoparticles, which can be combined with gene therapy, are of keen interest. This article discusses the development of bypass grafts, focusing on the optimization of the biological properties of mechanically suitable grafts.
