Prolonged exposure of colon cancer cells to the epidermal growth factor receptor inhibitor gefitinib （Iressa^TM） and to the antiangiogenic agent ZD6474： Cytotoxic and biomolecular effects

• Published in: World journal of gastroenterology : WJG 2006, Vol.12 (32), p.5140-5147
• Main Author: Amalia Azzariti Letizia Porcelli Jian-Ming Xu Grazia Maria Simone Angelo Paradiso
• Format: Article
• Language: English
• Subjects: ZD6474; 上皮生长因子; 生物分子; 细胞毒素; 结肠癌; 肿瘤细胞
• ISSN: 1007-9327; 2219-2840

AIM： To analyze the biological effects of prolonged in vitro exposure of HT-29 and LoVo colon cancer cell lines to gefitinib （Iressa^TM）, an inhibitor of epidermal growth factor receptor （EGFR） activity, and ZD6474, an inhibitor of both KDR and EGFR activities. METHODS： Cells were treated with each drug for up to 2 wk using either a continuous or an intermittent （4 d of drug exposure followed by 3 d of washout each week） schedule. RESULTS： In both cell types, prolonged exposure （up to 14 d） to gefitinib or ZD6474 produced a similar inhibition of cell growth that was persistent and independent of the treatment schedule. The effects on cell growth were associated with a pronounced inhibition of p-EGFR and/ or p-KDR expression. Treatment with gefitinib or ZD6474 also inhibited the expression of EGFR downstream signal molecules, p-Erkl/2 and p-Akt, although the magnitude of these effects varied between treatments and cell lines. Furthermore, expression of the drug resistance-related protein ABCG2 was shown to significantly increase after 14 d of continuous exposure to the two drugs. CONCLUSION： We conclude that long-term exposure of colon cancer cells to gefitinib and ZD6474 does not modify their cytotoxic effects but it might have an effect on sensitivity to classical cytotoxic drugs.