Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma Journal Article
| Authors: | Schwab, J.; Antonescu, C.; Boland, P.; Healey, J.; Rosenberg, A.; Nielsen, P.; Iafrate, J.; Delaney, T.; Yoon, S.; Choy, E.; Harmon, D.; Raskin, K.; Yang, C.; Mankin, H.; Springfield, D.; Hornicek, F.; Duan, Z. |
| Article Title: | Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma |
| Abstract: | Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. |
| Keywords: | protein kinase b; controlled study; human tissue; human cell; cisplatin; doxorubicin; drug efficacy; drug potentiation; antineoplastic agents; pyridines; cell proliferation; apoptosis; enzyme inhibition; protein kinases; in vitro study; tumor cells, cultured; pyrimidines; phosphatidylinositol 3 kinase; protein kinase inhibitors; cancer inhibition; blotting, western; cancer cell; mammalian target of rapamycin; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; upregulation; drug cytotoxicity; antibiotics, antineoplastic; chordoma; concentration response; pi3k; mtor; furans; pi-103; 2 (4 hydroxyphenyl) 4 morpholinopyrido[3',2':4,5]furo[3,2 d]pyrimidine; phosphoinositide dependent protein kinase 1 |
| Journal Title: | Anticancer Research |
| Volume: | 29 |
| Issue: | 6 |
| ISSN: | 0250-7005 |
| Publisher: | International Institute of Anticancer Research |
| Date Published: | 2009-01-01 |
| Start Page: | 1867 |
| End Page: | 1871 |
| Language: | English |
| PUBMED: | 19528441 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: ANTRD" - "Source: Scopus" |
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