Iressa (ZD 1839) Inhibits Phosphorylation of Three Different Downstream Signal Transducers in Head and Neck Cancer (SCCHN)

Abstract

Proliferation of squamous cell carcinoma of the head and neck (SCCHN) depends on epidermal growth factor receptor (EGFR) expression. The EGFR activates different signal pathways leading to gene transcription in the nucleus due to cell cycle progression and proliferation of tumor cells. AKT, STAT3 and MAPK play central roles in these pathways. However, they are not only regulated by the EGFR. We therefore investigated whether a specific inhibitor of the EGFR tyrosine kinase (ZD 1839 or Iressa) is able to inhibit phosphorylation of these three signals at the same time. Western blot analysis of pretreated SCCHN cells revealed that ZD 1839 greatly reduces the amount of phosphorylated AKT, STAT3 as well as MAPK. Surprisingly, this effect was not dose-dependent between the concentration range of 5.15 to 41.2 μM/ml. We conclude that Iressa has a high potency to inhibit nuclear gene transcription responsible for cell cycle progression. Furthermore, dose reduction of Iressa in the case of toxicity may not severely influence the response to treatment.