期刊
ORAL ONCOLOGY
卷 42, 期 4, 页码 430-439出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.oraloncology.2005.09.011
关键词
Akt; anoikis; apoptosis; KP372-1
资金
- NCI NIH HHS [1 P50 CA097007, P50 CA098258, P50 CA083639, P50 CA097007, P50 CA83639] Funding Source: Medline
- NIDCR NIH HHS [R01-DE14613, R01 DE014613] Funding Source: Medline
Therapies that target signaling pathways critical to the pathogenesis and progression of squamous cell carcinoma of the head and neck (HNSCC) are needed. One such target, phosphatidylinositol 3-kinase, and its downstream target serine/threonine kinase, Akt, are up-regulated in HNSCC. Targeted therapy could consist of inhibitors of these kinases or, alternatively, of inhibitors of the pathways that they regulate. To explore the effect of Akt inhibition on the growth and survival of HNSCC tumors, we evaluated the effect of a novel Akt inhibitor, KP372-1, on the growth, survival, and sensitivity to anoikis of HNSCC cell lines in culture. Using Western blotting of head and neck cancer cell tines and squamous mucosa and carcinoma specimens, we found that Akt was highly phosphorylated in head and neck cancer cell lines and human head and neck squamous carcinoma specimens. Treatment of HNSCC cell tines with KP372-1 blocked the activation of Akt, inhibited head and neck cancer cell proliferation, and induced apoptosis and anoikis in several HNSCC cell lines. Furthermore, KP372-1 decreased the phosphorylation of the S6 ribosomal (Ser240/244) protein, which is a downstream target of Akt. Taken together, these findings indicate that KP372-1 may be a useful therapeutic agent for HNSCC and should be further evaluated in preclinical models of HNSCC. (c) 2005 Elsevier Ltd. All rights reserved.
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