Figure 6

Inhibition of in vivo growth of pre-established tumor in xenograft model following the administration of SF1126 and its effect on proliferation and angiogenesis. A. Effect of SF1126 on the growth of the pre-established tumor in xenograft model. Athymic mice (n = 8-10) were subcutaneously implanted with the derivative glioma cells from ¹² V-Ha-Ras transgenic mice (5 ×10 ⁶ cells in 100 μl PBS per animal). Mice bearing comparable volumes of tumor (80–100 mm³) were treated with 50 mg/kg/dose of either SF1126 or vehicle 3 times weekly (Monday, Wednesday and Friday) for 3 weeks. B. IHC staining of PCNA confirming that treatment of tumors with SF1126 block proliferation of tumors in the V12-Ras glioma cell xenograft model. Bars represent Mean ± S.E. of the number of PCNA positive tumor cells per randomly chosen field at 40× magnification. *P < 0.05. Data is representative of three independent experiments (n = 3). C. IHC CD31 staining confirming that treatment of tumors with SF1126 block expression of CD31 in the tumor endothelial cells from the pre-established subcutaneous tumors. Bars represent Mean ± S.E. of the number of CD31 positive tumor cells per randomly chosen field at 20× magnification. *P < 0.02. Data is representative of three independent experiments (n = 4). D. Schematic representation of the proposed model for the mode of anti-tumor action of novel PI3-kinase inhibitor, SF1126 in glioma. Mechanism of action of SF1126 in the regulation of PI3-kinase pathway and MAP-kinase pathway in the derivative glioma cells from ¹² V-Ha-Ras transgenic mice is presented in the schematics.