Role of protein kinase C b and vascular endothelial growth factor receptor in XXXX : Therapeutic implications and the usefulness of @entity2199 model organism.

@entity2199 @entity5 @entity45817 @entity2615 @entity3620 @entity22988
PURPOSE: To examine the role of both protein kinase C (PKC)-b and vascular endothelial growth factor receptor (VEGFR)-2 in @entity3620 ( @entity3620 ) using respective inhibitors, @entity22988 and @entity45817 . MATERIALS AND METHODS: @entity3620 cell lines, control cells, and a variety of archived @entity5 samples were used to determine the protein expression levels of PKC-b, VEGFR-2, VEGF, and p-AKT. Effects of @entity22988 and @entity45817 on phosphorylation status of key signaling molecules and viability of the @entity2615 cells were determined. The common soil @entity2199 , @entity2199 , was treated with @entity22988 to determine its suitability to screen for highly potent kinase inhibitors. RESULTS: PKC-b1, PKC-b2 and VEGFR-2/KDR were overexpressed in @entity3620 cell lines and @entity5 tissues. @entity22988 treatment resulted in significant loss in viability of VEGF induced cell proliferation; however, the effect of @entity45817 was much less. @entity22988 also dramatically decreased the phosphorylation of PKC-b, its downstream target p-AKT, and surprisingly, the upstream VEGFR-2. The combination of the two drugs at best was additive and similar results were obtained with respect to cell viability. Treatment of @entity2199 with @entity22988 resulted in clear phenotypic changes and the worms were hypermotile with abnormal pattern and shape of eggs, suggesting altered fecundity. CONCLUSIONS: PKC-b1 and VEGFR-2 are both excellent therapeutic targets in @entity3620 . @entity22988 was better at killing @entity3620 cells than @entity45817 and the combination lacked synergy. In addition, we show here that @entity2199 can be used to screen for the next generation inhibitors as treatment with @entity22988 resulted in clear phenotypic changes that could be assayed.
