白藜芦醇对结肠癌大鼠果蝇WNT同源基因/β-连环蛋白信号通路的影响  

Effects of resveratrol on WNT homologous gene of drosophila/β-catenin signaling pathway in colon cancer rats

作　　者：莫安薇[1] 杨生辉[1] 黄琰菁[1] 王燕艳 MO An-wei;YANG Sheng-hui;HUANG Yan-jing;WANG Yan-yan(Department of Oncology,Hainan Provincial People's Hospital,Haikou 570000,Hainan Province,China)

机构地区：[1]海南省人民医院肿瘤内科,海南海口570000

出　　处：《中国临床药理学杂志》2021年第19期2631-2635,共5页The Chinese Journal of Clinical Pharmacology

基　　金：海南省自然科学基金资助项目(819MS117)。

摘　　要：目的探讨白藜芦醇对结肠癌大鼠果蝇WNT同源基因/β-连环蛋白(Wnt/β-catenin)信号通路的影响。方法用N-甲基-N-亚硝基脲灌肠构建结肠癌模型。将造模成功大鼠随机分为模型组、对照组和低、高剂量实验组,每组15只;另取15只正常大鼠作为空白组。空白组和模型组均灌胃给予0.9%NaCl_(2) mL,qd;低、高剂量实验组分别灌胃给予2.5和5.0 mg·mL^(-1)白藜芦醇溶液2 mL,qd;对照组尾静脉注射给予5.44 mg·mL^(-1)奥沙利铂溶液1 mL,每3周1次。5组大鼠均连续给药12周。比较各组的抑瘤率,用蛋白质印迹法测定肿瘤组织Wnt/β-catenin信号通路相关蛋白的表达水平。结果治疗后,低、高剂量实验组和对照组的抑瘤率分别为(35.42±3.71)%,(47.52±4.26)%和(57.24±6.04)%,低、高剂量实验组的抑瘤率与对照组比较,差异均有统计学意义(均P <0.05)。治疗后,低、高剂量实验组和对照组、模型组、空白组肿瘤组织的β-catenin相对表达量分别为1.74±0.23,1.38±0.17,1.14±0.15,2.53±0.34和0.58±0.08,TCF-4相对表达量分别为1.89±0.25,1.67±0.23,1.25±0.17,2.62±0.36和0.64±0.09,C-myc相对表达量分别为1.82±0.22,1.53±0.21,1.21±0.14,2.59±0.37和0.61±0.07,Cyclin D1相对表达量分别为1.78±0.21,1.57±0.22,1.33±0.18,2.49±0.35和0.52±0.07。模型组的上述指标与低、高剂量实验组和空白组、对照组比较,差异均有统计学意义(均P <0.05)。结论白藜芦醇能够剂量依赖性地抑制结肠癌大鼠肿瘤组织生长,其作用可能与抑制Wnt/β-catenin信号通路激活有关。Objective To analyze the effect of resveratrol on WNT homologous genes of drosophila/β-catenin(Wnt/β-catenin) signaling pathway in colon cancer rats.Methods The colon cancer model was established by using N-methyl-N-nitroso urea enema.The model rats were randomly divided into model group,control group and experimental-L,-H groups with 15 rats per group.Another 15 normal rats were taken as blank group.Blank and model groups were given 0.9% NaCl_(2) mL by gavage,qd.Experimental-L,-H groups were given 2.5 and5.0 mg·mL^(-1) resveratrol solution 2 mL by gavage,qd.Control group was given oxaliplatin solution 1 mL by tail vein injection,once every 3 weeks.Five groups were treated for 12 weeks.The tumor inhibition rate of each group was compared.The expression levels of Wnt/β-Catenin signaling pathway related proteins in tumor tissue were measured by Western blot.Results After treatment,the tumor inhibition rates in experimental-L group,experimental-H group and control group were(35.42±3.71) %,(47.52±4.26) % and(57.24±6.04) %.The tumor inhibition rates of the experimental-L,-H groups were significantly different from that of control group(all P <0.05).After treatment,the relative expressions of β-catenin protein in tumor tissue of experimental-L,experimental-H,control,model and blank groups were 1.74±0.23,1.38±0.17,1.14±0.15,2.53±0.34 and0.58±0.08,the relative expressions of TCF-4 were 1.89±0.25,1.67±0.23,1.25±0.17,2.62±0.36 and0.64±0.09,the relative expressions of C-myc were 1.82±0.22,1.53±0.21,1.21±0.14,2.59±0.37 and0.61±0.07,the relative expressions of CyclinD1 were 1.78±0.21,1.57±0.22,1.33±0.18,2.49±0.35 and0.52±0.07.The above-mentioned indexes in the model group were significantly different from those in experimental-L,experimental-H,control and blank groups(all P <0.05).Conclusion Resveratrol can inhibit tumor growth in colon cancer rats in a dose-dependent manner,which may be related to the inhibition of Wnt/β-catenin signaling pathway activation.

关 键 词：白藜芦醇 结肠癌 大鼠 血管内皮细胞生长因子 转移相关黏附分子CD44V6 果蝇WNT同源基因/β-连环蛋白信号通路 

分 类 号：R28[医药卫生—中药学]