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 lines 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 lines 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.