The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating PI3K/AKT pathway

Abstract PURPOSETo study the effect of the embryonic stem cell (ESc) microenvironment in inhibiting mouse glioma cells and its possible mechanism. METHODSGlioblastoma cell line U118 in the brain, was investigated in this study. There were four experimental groups: U118 glioma cells cultured alone as the control group (GB group), U118 cell and ESc co-cultured group(GE group), U118 cell and ESc co-cultured and adding phosphoinositide 3-kinase (PI3K) agonist group (GA group), U118 and temozolomide as the positive control group (GT group); U118 cells were harvested after 72 hours of culture. Cell proliferation, apoptosis, reactive oxygen species (ROS) and vasculogenic mimicry assays, quantitative real-time RT-PCR (qPCR), and western blot (WB) were study, the biological function of U118 glioma cells and the PI3K/AKT signaling pathway were compared the differences between the groups. RESULTSCompared with the GB control group, the GE co-culture group and GT chemotherapy group showed reduced cell proliferation, increased apoptosis, increased ROS, decreased or disappearance of vasculogenic mimicry. Expression of cyclin B and D, significantly reduced, while that of BAX, BCL-2, P53, Caspase3, Gsk-3B, P21, and P27, significantly increased. The expression of PI3K, PDK, AKT, and mTOR, significantly decreased while that of PTEN significantly increased. The expression of positive regulatory factors significantly increased but negative regulatory factors decreased in GA group compared to the GE group. CONCLUSIONThe ESC microenvironment reverse glioma malignancy, partially via inhibition of the PI3K signaling pathway. Our study may have a significant impact and clinical implication on cell therapy in glioma.