Apoptosis and growth inhibition of head and neck tumor cell line induced by epidermal growth factor receptor tyrosine kinase inhibitor

Overexpression of the epidermal growth factor (EGF) receptor, a hallmark of aerodigestive squamous cell carcinoma of the head and neck (SCCHN), correl ates with aggressive tumor behavior. There is evidence that SCCHN cells aut o-activate their EGF receptors. The receptor has therefore attracted intere st as a potential therapeutic target. We tested the in vitro therapeutic ef ficacy of PD153035-a potent, specific inhibitor of the tyrosine kinase intr insic to the EGF receptor-by employing a well-characterized cell line deriv ed from human gingival SCCHN. DNA-synthesis and cell number were assayed fo r growth-inhibitory effects, phosphorylation of the EGF receptor was quanti tated by immunoblot, and cell apoptosis was detected by terminal deoxytrans ferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labe ling (TUNEL) in situ assay. PD153035, at nanomolar concentrations, inhibite d autophosphorylation of the EGF receptor induced by EGF stimulation and th e inhibition occurred in a dose-dependent manner. Under the same conditions , PD153035 inhibited cell growth, and induced apoptosis of SCCHN cells in v itro. We conclude that selective inhibition of the EGF receptor tyrosine ki nase completely abolishes EGF receptor phosphorylation resulting from recep tor stimulation, and results in growth inhibition and apoptosis of SCCHN ce lls in vitro. By inducing cytostasis and apoptosis, this new class of inhib itors may be of therapeutic value against SCCHN. (C) 1999 Elsevier Science Ltd. All rights reserved.