Otes tumor growth, invasion and metastasis. 13 As MMP also plays an R Crucial role in Invasivit t and metastatic cancers, the inhibition of these pathways is also the reinforcing Useful ndnis of cancer. ITG 1 and DDR2 expression PI3K AKT Signaling Pathways of genes may need during the interaction with fibril Re upregulated collagen. That the silence of ITG has an effect on the expression of genes, DDR2, and vice versa, had l Sst suggests that gene expression of both proteins is To another. This coupling is not at the level of PKC, as PKC inhibition only had an effect on the expression of DDR2, but not on ITGa1, reduced levels of gene expression of ITG 1 after treatment with an inhibitor of FAK. If the relationship between DDR2 and ITGa1 takes place remains to be investigated.
The present study showed that direct contact between chondrocytes and increased collagen ht Both MMP gene expression 13 and collagenolytic activity t. The maintenance of maternal perizellul Ren matrix of chondrocytes prevents collagen-induced upregulation of MMP-13. Both DDR2 and modulate the expression of MMP ITGa1 13 in a direct contact between chondrocytes and collagen. On interaction Varespladib with collagen receptors, PKC plays a role The very important, probably through the activation of PYK2. In addition, we have shown that are involved in both the MEK / ERK and JNK in the expression of collagen-stimulated MMP 13th The expression of DDR2 is mediated by PKC and the expression of FAK by ITGa1. EPC outgrowth endothelial cells were treated with TAE226 for 1 week, or the combination of RAD001 determine the effect of these drugs on the proliferation and differentiation treated.
Fibroblasts and tumor cells served as controls. The data represent three independent Independent experiments, each performed in duplicate. The numbers of the OEC, were EC-EPC, fibroblasts and tumor cells derived compared to contr L by the two drugs in a dose- Reduced ngigen way. Sensitivity to 100 nM was TAE226 at the h Chsten the tumor cells and HT29 OEC with a share of lebensf HIGEN cells by 38% and 6422 9%, respectively. IC50 values were calculated at 45 nm and 324 nm, respectively. This reflects the gr Ere CSB sensitivity at low concentrations of TAE226 against the EPC. Differentiation of the EPC to EC was less inhibited.
The treatment with 1 mM EPC TAE226 has entered Born a reduction in EC differentiation 2317th In order to investigate the effect of TAE226 on fibroblast proliferation, was used as a control For the non-tumor tissue and non-endothelial cells. The fibroblasts are less sensitive to TAE226 suggesting a specific effect of TAE226. Treatment with RAD001 has entered Born potent inhibition of EPC and OEC compared to fibroblasts and HT29 cells. EPC were the most sensitive cell type of the CSB with an IC50 value followed by 27 nm. HT29 tumor cells were less sensitive. There was no significant inhibition of the proliferation of fibroblasts at 200 nm RAD001. The incubation with 20 nM RAD001 reduced the percentage of lebensf HIGEN EPC and OEC be derived EC after 1 week of treatment in 4831 34% and 36%. However, 100 nM of the drug was necessary to obtain a Similar inhibition of HT29 cells. Maximum inhibition of HT29 cells was only in 4023 reached% to 1000 nm. It is noteworthy that there are already 200 nM RAD001 sufficient to inhibit the differentiation of the EPC EC powerful with only 1310% of lebensf HIGEN cells. Treatmen