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

作     者：Amalia Azzariti Letizia Porcelli Jian-Ming Xu Grazia Maria Simone Angelo Paradiso 

作者机构：Clinical Experimental Oncology Laboratory National Cancer Institute Bari Italy Beijing 307 Hospital Cancer Center Beijing 100039 China 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2006年第12卷第32期

页      面：5140-5147页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by grants from the Italian Association for Cancer Research (AIRC-2004)from the Italian Ministry of Health Project ex art.12  Region of Emilia Romagna RF02 

主　　题：Gefitinib ZD6474 Colon cancer Tyrosine ki-nase Chemo-resistance 

摘      要：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.