pi103 and Chordoma

Chordomas are rare tumors of the axial skeleton for which surgical resection remains the most reliable means of cure. PI-103 is a inhibitor of PI3K/AKT and mTOR activation. This study aims to determine whether the PI3K/mTOR pathway was active in chordomas and whether their inhibition could lead to decreased proliferation and increased apoptosis.. Thirteen human chordoma were tested for activation of the PI3K/mTOR pathway. The human chordoma cell line UCH-1 was treated with increasing doses of PI-103. Inhibition of AKT and mTOR was examined and assays assessing proliferation and apoptosis were performed.. The chordoma specimen demonstrated activation of the PI3K/mTOR pathway. PI-103 inhibited the AKT and mTOR activation in the UCH-1 cell line. PI-103 inhibited proliferation and induced apoptosis in UCH-1.. The PI3K/AKT and mTOR signaling pathway is constitutively activated in chordoma. PI-103 decreases proliferation and induces apoptosis in the UCH-1 via inhibition of the PI3K/mTOR pathway.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Proliferation; Chordoma; Cisplatin; Doxorubicin; Furans; Humans; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Kinase Inhibitors; Protein Kinases; Proto-Oncogene Proteins c-akt; Pyridines; Pyrimidines; TOR Serine-Threonine Kinases; Tumor Cells, Cultured