LY294002

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LY294002 is an effective inhibitor of various proteins and a potent inhibitor of PI3K. GLUT1 is often overexpressed in cancer, and studies have shown that activation of AKT promotes GLUT1 expression on the plasma membrane. While inhibition of AKT does not lead to decreased GLUT1 expression, treatment with the PI3K inhibitor LY294002 results in a significant decrease in GLUT1.
PI3K is responsible for coordinating various cellular functions, including proliferation, cell survival, and cell migration. LY294002 can inhibit cellular migration activity. The PI3K inhibitor LY294002 can block PI3K/AKT signaling, further inhibiting glycolysis, disrupting ATP production, and ultimately inducing apoptosis.
The PI3K inhibitor LY294002 may offer a new therapeutic approach to counteract resistance caused by sorafenib. Sorafenib, as a small molecule tyrosine kinase inhibitor, is clinically used to treat acute myeloid leukemia with internal tandem duplication mutation of the fms-like tyrosine kinase 3 (FLT3-ITD).
LY294002 was observed to induce more apoptosis in sorafenib-resistant cells than in parental cells in FLT3-ITD mutated cell lines.
LY294002 increases the sensitivity of cancer cells to chemotherapy-induced apoptosis by enhancing the expression of DR4 and DR5, as well as the activation of caspase-8 and -3. Additionally, LY294002-mediated chemotherapy sensitivity involves mitochondrial Bax translocation and cytoplasmic cytochrome c accumulation. Independent of Akt inhibition, LY294002 promotes dephosphorylation of cells at serine 9 residue, leading to the reactivation of glycogen synthase kinase 3beta (GSK3β).