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中国癌症防治杂志 ›› 2020, Vol. 12 ›› Issue (1): 28-33.doi: 10.3969/j.issn.1674-5671.2020.01.05

• 基础研究 • 上一篇    下一篇

高脂饮食对结肠癌肝脏转移的影响及作用机制

  

  1. 云南省第一人民医院/昆明理工大学附属医院普外一科;650500 昆明 2昆明理工大学医学院
  • 出版日期:2020-02-25 发布日期:2020-03-10
  • 通讯作者: 赵泉 E-mail:zhaoquan_123@126.com

 Effect of high-fat diet on liver metastasis of colon cancer and its underlying mechanism

  • Online:2020-02-25 Published:2020-03-10
  • Supported by:
    云南省科技计划项目[2017FE467(-119)];云南省卫生科技计划项目(2017NS208);云南省卫生和计划生育委员会医学学科带头人培养计划项目(D-201656)

摘要: 目的 探讨高脂饮食对结肠癌肝脏转移的影响及其作用机制。方法 30只NSI第三代免疫缺陷裸鼠脾脏种植结肠癌细胞DLD1构建移植瘤裸鼠模型,分别喂养普通饲料(对照组)、高脂饲料(高脂饮食组)和高脂饲料并腹腔注射CXCR4拮抗剂AMD3100(高脂饮食+AMD3100组),每组10只。12周后颈椎脱臼处死,称量各组裸鼠体重、肝脏重量,统计肝脏中肿瘤转移灶数目,并采用Western blot和RT-qPCR检测肿瘤组织中SDF-1、CXCR4的蛋白和mRNA表达水平。结果 12周后,高脂饮食组裸鼠体重、脂肪重量、肝脏重量及血清瘦素浓度高于对照组和高脂饮食+AMD3100组(P<0.05)。对照组、高脂饮食组和高脂饮食+AMD3100组裸鼠发生肝脏转移的比例分别为30.0%、80.0%和40.0%。高脂饮食组裸鼠的肿瘤体积及肝脏转移灶数量均明显高于对照组[(3.83±0.42) mm3  vs (1.00±0.15) mm3P<0.001;(4.33±0.58) 个 vs (1.33±0.58) 个,P=0.002]和高脂饮食+AMD3100组 [(3.83±0.42) mm3  vs (1.96±0.15) mm3P<0.001;(4.33±0.58) 个 vs (2.33±0.58) 个,P=0.002]。Western blot和RT-qPCR检测结果显示,高脂饮食组结肠癌组织中的SDF-1、CXCR4的蛋白和mRNA表达水平均较对照组和高脂饮食+AMD3100组明显上调(均P<0.05)。结论 高脂饮食可通过促进结肠癌癌组织中SDF-1和CXCR4的表达水平而增强结肠癌的肝脏定向转移。

关键词: 结肠癌, 高脂饮食, 肝脏转移, SDF-1, CXCR4

Abstract: Objective  To investigate the effect of high-fat diet on liver metastasis of colon cancer and its underlying mechanism. Methods Xenograft models of nude mice were constructed based on the data of a total of 30 NSI third-generation immunodeficient nude mice,which were implanted with colon cancer cells DLD1 into their spleens. The xenograft nude mice were evenly divided into three groups:a control group,which was fed normal diet,a high-fat diet group,which was fed high-fat diet,and a high-fat diet+AMD3100 group,which was fed high-fat diet with intraperitoneal injection of CXCR4 antagonist AMD3100.  After 12 weeks,the nude mice in each group were sacrificed by cervical dislocation,and the weights of the bodies and livers of nude mice were monitored,and the number of tumor metastasis in the liver was counted. The protein and mRNA expression of SDF-1 and CXCR4 in tumor tissues of each group were detected by Western blot and RT-qPCR. Results After 12 weeks,the body weight,fat mass,liver weight,and serum leptin concentration of the nude mice in the high-fat diet group were significantly higher than those in the control group and the high-fat diet+AMD3100 group(P<0.05). The proportion of liver metastasis in the control group,high-fat diet group,and high-fat diet+AMD3100 group nude mice were 30.0%,80.0%,and 40.0%,respectively. The tumor volume and the number of liver metastases in the high-fat diet group were significantly higher than those in the control group [(3.83±0.42) mm3 vs (1.00±0.15) mm3P<0.001; 4.33±0.58 vs 1.33±0.58,P=0.002] and the high-fat diet+AMD3100 group [(3.83±0.42) mm3 vs (1.96±0.15) mm3P<0.001; 4.33±0.58 vs 2.33±0.58,P=0.002]. Western blot and RT-qPCR results showed that the protein and mRNA expression of SDF-1 and CXCR4 in colon cancer tissues in the high-fat diet group were significantly higher than those in the control group and the high-fat diet+AMD3100 group(P<0.05). Conclusion High-fat diet can enhance liver metastasis of colon cancer by promoting the expression of SDF-1 and CXCR4 in colon cancer tissues. 

中图分类号: 

  • Colon cancer