C. Representative areas are shown (× 400 magnification). TUNEL-positive cells in orthotopic tumor xenografts (Lift: no treatment group; Right: treatment with 75 mg/kg LY2940020). D. Apoptosis rate induced by different concentrations of LY294002 in tumors xenografts in athymic nude mice. Immunohistochemical studies

for xenograft tumor tissues Finally, the histological examination and immunohischemistry were performed to determine the biological influence of LY294002 on tumor morphology, proliferation, apoptosis, and expression of Akt, phosphorylated Akt. The histological changes showed that tumor cells of treated groups were more necrosis than those of control group (Fig 5A). Compared with control group, the expression of phosphorylated Akt was significantly decreased in treated with LY294002 (Fig 5B). Results of immunohistochemical staining with Ki67 and caspase-9 support the gross observations. selleck screening library A great many of NPC cells from the control group stained positive Ki67 (Fig 5C). The number of proliferation cells treated with LY29400 showed significant reduction in a dose-dependent manner (Fig 5D), with significant difference (P < 0.05; P < 0.01). The expression of caspase-9 appeared to have an obvious increase in the groups treated with LY294002 (Fig 5E). No significant difference was found

between the expression of Akt in tumor from the control and LY294002-treated mice. Figure 5 Histological examination and immunohischemistry analysis of tumors xenografts in athymic nude mice. A Representative areas are shown (× 200 magnification). Histological appearance Tobramycin of tumor tissue from CNE-2Z-inoculated athymic Natural Product Library price mice with or without

PI3K inhibitor treatment (Left: no treatment group; Right: treatment with 75 mg/kg LY2940020). B Expression of p-Akt in the tumor tissue with or without PI3K inhibitor treatment (Left: no treatment group; Right: treatment with 75 mg/kg LY2940020). C Expression of Ki67 in the tumor tissue with or without PI3K inhibitor treatment (Left: no treatment group; Right: treatment with 75 mg/kg LY2940020). D Expression of caspase-9 in the tumor tissue with or without PI3K inhibitor treatment (Left: no treatment group; Right: treatment with 75 mg/kg LY2940020). Discussion The PI3K/Akt cascade is known to be an important survival factor in the signal transduction cascades involved in the cell survival and apoptosis. PI3K is one of the core intracellular signaling molecules in the stimulation of growth factors, subsequently phosphorylating and activating Akt. This signaling pathway cascades activated by some other factors play a critical role in regulating tumor cell growth, survival, motility, invasion, and differentiation. Although there has been a rapid expansion in the number of identified physiological Akt substrates that are involved in various aspects of cellar function, there are clearly candidates that are directly involved in the regulation of apoptosis [2].