Therapeutic and Preventive Effects of an Epidermal Growth Factor Receptor Inhibitor on Oral Squamous Cell Carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is the sixth most common human neoplasm worldwide. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is highly expressed in human OSCC and is a target for cancer therapy and prevention. This study investigated the therapeutic and preventive effects of an inhibitor of EGFR (PD153035) on OSCC. The effects of PD153035 were examined in human cancer cell lines in vitro, in an athymic nude mouse xenograft model in vivo, and in the 7,12-dimethyl benz[a]anthracene (DMBA)-induced hamster cheek pouch tumour model in vivo. PD153035 significantly inhibited cell growth, delayed cell cycle progression and induced apoptosis in human OSCC cells in vitro. In vivo, PD153035 inhibited xenograft tumour growth in nude mice in a dose-dependent manner and prevented the development of OSCC at the postinitiation stage in the DMBA-induced hamster cheek pouch tumour model. PD153035 inhibited the DMBA-induced increases in cell proliferation and in levels of phosphorylated EGFR and phosphorylated signal transducer and activator of transcription 3 (STAT3) protein in the hamster cheek pouch. Inhibitors of EGFR, such as PD153035, have potential value in the treatment and prevention of OSCC.