• Joseph Schwab, Cristina Antonescu, Patrick Boland, John Healey, Andrew Rosenberg, Petur Nielsen, John Iafrate, Thomas Delaney, Sam Yoon, Edwin Choy, David Harmon, Kevin Raskin, Cao Yang, Henry Mankin, Dempsey Springfield, Francis Hornicek, and Zhenfeng Duan.
• Department of Orthopedic Surgery, Section of Orthopedic Oncology, Sarcoma Research Laboratory, Massachusetts General Hospital, Boston, MA 02114, U.S.A. jhschwab@partners.org
• Anticancer Res. 2009 Jun 1; 29 (6): 1867-71.

BackgroundChordomas 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.Materials And MethodsThirteen 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.ResultsThe 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.ConclusionThe 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.

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