Docetaxel significantly inhibited tumor growth, and the tumor vol ume on day 70 was slightly larger than the average tumor volume determined when treatment was initiated. Tumors from mice treated with si Vav3 plus Nintedanib Inhibitors,Modulators,Libraries docetaxel were statistically smaller than those from mice treated with docetaxel alone, and the tumor volume on day 70 was 59% smaller than that when treatment was initiated. It appears reasonable to suppose that a lower concentration of docetaxel can be used in combin ation therapy with si Vav3 because wide differences were not observed between these two groups despite the stat istical significance of the differences. In addition, during a 70 day observation period, we did not note any toxicity in mice treated with si Vav3 plus docetaxel, as evaluated by their body weights and physical Inhibitors,Modulators,Libraries appearance.

These results in tumor xenografts support the data of the combined effect of si Vav3 with docetaxel on cancer cell growth in vitro. On day 70 after inoculation, tumor tissues were harvested from euthanized mice and subjected to immu noblot analysis of Vav3, Inhibitors,Modulators,Libraries H E staining and immunohisto chemical staining Inhibitors,Modulators,Libraries of Vav3, Ki 67, pAR, and a commercially available cell death marker, M30 CytoDeath. Treatment with si Vav3 effectively downregulated Vav3 expression compared with its expression level in control and si Scr treated tumors, illustrating the effectiveness of intra tumoral injection. Histological evaluation revealed that docetaxel alone or si Vav3 plus docetaxel caused necrosis in some areas of xenograft tumors.

Significant downregulation of Vav3 staining was observed in tumors from mice treated with si Vav3 alone or in combination with docetaxel but not in tumors from mice treated with docetaxel alone. Repre sentative immunohistochemical staining of Ki 67, pAR, and M30 CytoDeath is Inhibitors,Modulators,Libraries shown in Figure 5D, and the immu nohistochemical findings are summarized in Figure 5E. The mean percentage of Ki 67 positive tumor cells in si Vav3 or docetaxel treated tumors was significantly de creased compared with that in control tumors, and an even more significant reduction was observed in tumors treated with si Vav3 plus docetaxel. A significant decrease in the number of pAR positive cells was observed in tumors treated with si Vav3 alone or in combination with docetaxel compared with the number of pAR positive cells in control tumors but not in tu mors treated with docetaxel alone. The average apoptotic index for the control tumors was 0. 4 0. 1% compared with 8 5% and 24 8% in tumors from mice treated with si Vav3 and docetaxel, respectively. Tumors from mice treated with the combin ation of si free overnight delivery Vav3 and docetaxel exhibited the highest apop totic index, which was significantly greater than that in control tumors.