Inhibition of Akt kinase signalling and activation of Forkhead are indispensable for upregulation of FasL expression in apoptosis of glioma cells

摘要: Activation of Akt signalling pathway is frequently found in glioma cells and may contribute to their resistance undergo apoptosis response conventional therapies. We that cyclosporin A (CsA) induces C6 cells, which associated with transcriptional activation fasL. In the present paper, we investigated an involvement regulation FasL expression CsA-induced apoptosis. demonstrated level active decreases significantly after CsA treatment, results decrease Forkhead phosphorylation its translocation nucleus. It correlated increase binding Forkhead-responsive element FHRE from promoter, as by gel-shift assays. Although treatment LY294002, a specific inhibitor PI3 K, decreased increased Fkhr nucleus, these events were not sufficient induce cells. Interference Akt/Forkhead membrane-targeted or removal FKHR-binding sites promoter abolished activation. These indicate downregulation prerequisite for induction promoter. be clinically important pharmacological intervention gliomas.