http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7110 Norcantharidin has been used as an efficacious anticancer drug in China for many years, but its true mechanism remains poorly understood. Intriguingly, in an in vitro series study of anticancer drugs, we found that norcantharidin can effectively inhibit epithelial tumor cells from expressing integrin αvβ6. Our previous studies have confirmed that integrin αvβ6 is closely relevant to malignant epithelial cell tumor biology behavior, and it can promote cancer cells to invade and metastasize through a special αvβ6–extracellular signal-related kinase (ERK) direct signaling pathway. In this study, we investigated the relationship between the norcantharidin anticancer mechanism and integrin αvβ6. After HT-29 colon cancer cells were treated with norcantharidin,cell apoptosis increased remarkably. The expression of αvβ6 and the amount of p-ERK decreased substantially; simultaneously, the linkage between αvβ6 and ERK was barely detectable. However, the expression of other integrins and the levels of mitogen-activated protein kinase hardly changed. On these grounds, we presumed that norcantharidin induced HT-29 colon cancer cell apoptosis through the αvβ6–ERK signaling pathway. This finding elicited a novel strategy for targeting the whole αvβ6–ERK signal pathway, rather than simply blocking the combining site of αvβ6–ERK in colon cancer treatment. 2011-02-02T22:40:16.820Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5428 Integrin αυβ6 plays a very important role in the progression of colon cancer cells and is now defined as a novel, independent prognostic indicator for aggressive colon cancer in humans. Herein, we use the RNA interfering technology to downregulate the expression of αυβ6 in colon cancer cells. Our data demonstrate that plasmid vector based shRNA can effectively down-regulate αυβ6 expression in protein and mRNA levels. Supression of integrin αυβ6 inhibits the phosphorylation and nonphosphorylation level of ERK1/2, the secretion of uPA, pro-MMP-9 and pro-MMP-2 in tumor conditioned medium, and more important, inhibits MAPKdependent [³H] labeled collagen IV degradation via the plasminogen activation cascade. Our study demonstrates in vitro that supression of integrin αυβ6 inhibits extracellular matrix degradation through the MAPK pathway. 2010-04-27T04:48:41.233Z ]]>