胰岛素对化疗药物5-氟尿嘧啶的增效作用及其机制

Insulin-induced Enhancement of Chemotherapeutic Response of 5-Fluorouracil and Its Mechanism

摘要: 目的建立裸鼠人食管癌模型,观察胰岛素是否增强5-氟尿嘧啶(5-Fu)对裸鼠的化疗疗效并探讨其机制。方法免疫组织化学方法检测肿瘤组织中CyclinD1的表达。ELISA方法检测裸鼠血清中胰岛素样生长因子(IGF-1)和胰岛素样生长因子结合蛋3(IGFBP-3)含量变化。结果大中小剂量胰岛素(0.09、0.06、0.03u/20g)均可明显增强5-Fu的抑瘤作用(P<0.05),但并不增加5-Fu的毒副反应。胰岛素组与对照组相比,CyclinD1表达水平明显增多(P<0.05)。5-Fu组和联合用药组之间IGF-I和IGFBP-3水平差异无统计学意义(P>0.05)。结论在裸鼠人食管癌模型中,胰岛素能增强5-Fu对裸鼠人食管癌移植瘤的化疗疗效,CyclinD1表达水平增多在胰岛素增效机制中发挥着重要作用。而血清中IGF-I和IGFBP-3含量变化尚不能解释其增效机制。

Abstract: Objective To observe whether insulin can induce an enhancement of chemotherapeutic response of 5-fluorouracil (5-Fu) on human transplantable esophageal cancer nude model and study the mechanism of action. Methods The expression of cyclin D_1 in tumor tissue was tested by immunohistochemistry. Murine serum insulin-like growth factor1(IGF-1) and insulin-like growth factor binding protein3(IGFBP-3) were determined by ELISA. Results High, medium and low dose insulin ( 0.09, 0.06, 0.03 u/20g) combined with 5-F...