Antisense epidermal growth factor receptor delivered by adenoviral vector blocks tumor growth in human gastric cancer

Epidermal growth factor receptor (EGFR) protein overexpression is commonly found in human gastric cancer, and its gene amplification is known to corre late with poor prognosis in gastric cancer patients. With regard to therapy trials targeting EGFR, it has been reported that stable transfection of EG FR antisense or treatment with antibody against EGFR results in growth supp ression of human cancer cells that express high levels of ECFR. We have des igned an adenovirus-expressing antisense ECFR and have investigated its eff ect on the growth of gastric cancer in vitro and in vivo. Following infecti on with EGFR antisense RNA-expressing adenovirus (Ad-EAS), the cell surface ECFR protein levels of infected cancer cells were markedly reduced, and th e in vitro growth of Ad-EAS-infected cells was significantly inhibited rela tive to control-infected cells in all three gastric cancer cell lines (AGS, KKLS, and MKN28) studied here (P < .0002). In a nude mouse subcutaneous tu mor system, in vivo tumor growth of MKN28 was significantly inhibited after Ad-EAS treatment, and inhibition on day 48 was 93% by volume compared with that of untreated controls. These results suggest that an adenoviral vecto r system targeting the down-regulation of EGFR could be a good candidate fo r the therapy of gastric cancers that overexpress EGFR.