5-氟尿嘧啶激活 TGF-β1／Smad 通路治疗结肠癌的机制研究

摘要

Objective To explore the action mechanism of 5-fluorouracil ( 5-Fu ) in treatment of colon cancer by activating TGF-β1/Smad pathway .Methods A total of 24 male Wistar rats were randomly divided into control group , azoxymethane treatment group ( AOM group ) , AOM plus 5-Fu treatment group ( AOM +5-Fu group ) , with 8 rats in each group.The expression levels of transforming growth factor-β1 (TGF-β1),TGF-βtypeⅡreceptor (TGF-βRⅡ) and Smad4 of Smad gene family members were detected by Real-time quantitative PCR , Western Blot and immunohistochemistry , respectively.Results As compared with those in control group , the expression levels of TGF-β1 mRNA,TGF-βR Ⅱ mRNA and Smad4 mRNA were significantly decreased ( P <0.01).As compared with those in AOM group, the expression levels of TGF-β1, TGF-βRⅡand Smad4 were significantly increased ( P <0.01) after 5-Fu treatment.Conclusion The 5-Fu can increase the expression levels of TGF-β1, TGF-βRⅡand Smad4 in colon cancer tissues to activate TGF-β1/Smad pathway.%目的：探讨5-氟尿嘧啶（5-Fu）通过激活转化生长因子β1／Smad（TGF -β1／Smad）通路治疗结肠癌的机制。方法将24只雄性Wistar大鼠随机分为正常对照组，氧化偶氮甲烷处理组（ AOM组）和AOM及5-Fu处理组（ AOM＋5-Fu组），每组8只。通过实时定量PCR、免疫印迹及免疫组织化学方法观测5-Fu处理后结肠癌组织中TGF-β1及其Ⅱ型受体（ TGF-βRⅡ）和下游Smad基因家族成员Smad4表达的变化。结果与对照组大鼠相比，AOM组大鼠TGF-β1 mRNA、TGF-βRⅡmRNA和Smad4 mRNA的表达显著降低（ P ＜0．01）；与AOM组大鼠相比，AOM＋5-Fu组TGF-β1 mRNA、TGF-βRII mRNA和Smad4 mRNA的表达显著增加（ P ＜0．01），但没有恢复到对照组水平。与对照组大鼠相比，AOM组大鼠TGF-β1、TGF-βRⅡ和Smad4与β-actin的比值显著降低（ P ＜0．01）；与AOM组大鼠相比， AOM＋5-Fu组处理后TGF-β1、TGF-βRⅡ和Smad4与β-actin的比值显著增加（ P ＜0．01），但没有恢复到对照组水平。与对照组大鼠相比，AOM组大鼠TGF-β1、TGF-βRⅡ和Smad4的AOD值显著降低（ P ＜0．01）；与AOM组大鼠相比，AOM＋5-Fu组处理后TGF-β1、TGF-βRⅡ和Smad4的AOD值显著增加（ P ＜0．01），但没有恢复到对照组水平。结论5-Fu能够提高结肠癌组织中TGF-β1，TGF-βRⅡ和Smad4的表达，激活了TGF-β1／Smad通路。