CC-223 inhibits human head and neck squamous cell carcinoma cell growth
2018
Wang, Jun-ying | Jin, Xin | Zhang, Xin | Li, Xiao-feng
mTOR over-activation is associated with the progression of head and neck squamous cell carcinoma (HNSCC). CC-223 is a novel and potent mTOR kinase inhibitor. Its activity against human HNSCC cells is studied here. In established SCC-9 cells and primary human oral cavity carcinoma (OCC) cells, CC-223 treatment at only nM concentrations significantly inhibited survival, proliferation and cell cycle progression. Furthermore, CC-223 provoked apoptosis activation in human HNSCC cells. CC-223 is more efficient in killing HNSCC cells than other known Akt-mTOR inhibitors: RAD001, MK-2206 and AZD-2014. CC-223 was however non-cytotoxic to the primary human oral epithelial cells. Further studies demonstrate that CC-223 almost completely blocked mTOR complex 1 (mTORC1) and mTORC2 activation in SCC-9 cells and primary OCC cells. In vivo, oral administration of CC-223 at well-tolerated doses potently inhibited SCC-9 xenograft tumor growth in severe combined immunodeficient mice. mTORC1 and mTORC2 activation was largely inhibited in CC-223-treated tumor tissues. Overall, targeting the mTOR kinase by CC-223 inhibits human HNSCC cell growth in vitro and in vivo. CC-223 might have a translational value for the treatment of HNSCC.
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