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.
瞄准：为了分析 HT-29 和 LoVo 结肠癌房间的延长在试管内暴露的生物效果，排队到 gefitinib (Iressa ) ，表皮的生长的一个禁止者因素受体(EGFR ) 活动，和 ZD6474， KDR 和 EGFR 活动的一个禁止者。方法：房间用也为多达 2 wk 与每药被对待一连续或一断断续续(药暴露的 4 d 每个星期由冲刷的 3 d 列在后面) 时间表。结果：在两种细胞类型，延长了暴露(多达 14 d ) 到 gefitinib 或 ZD6474 生产了治疗时间表坚持、独立的细胞生长的类似的抑制。房间生长上的效果与 p-EGFR 或 p-KDR 表示的显著抑制被联系。有 gefitinib 或 ZD6474 的治疗也禁止了 EGFR 下游的信号分子， p-Erk1/2 和 p-Akt 的表达式，尽管这些效果的大小在治疗和房间线之间变化了。而且，抵抗相关的蛋白质 ABCG2 被显示出显著地在连续暴露的 14 d 以后增加到二药的药的表示。结论：我们断定到 gefitinib 和 ZD6474 的结肠癌房间的长期的暴露不修改他们的细胞毒素的效果，但是它可能在敏感上有效果到古典细胞毒素的药。
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
