实用肿瘤学杂志 ›› 2020, Vol. 34 ›› Issue (2): 163-168.doi: 10.11904/j.issn.1002-3070.2020.02.014

• 基础研究 • 上一篇    下一篇

建立结直肠癌移植瘤模型研究小鼠肠道中细菌感染情况及地西他滨联合顺铂化疗的作用机制

李斌, 冯保恒, 尹富霞, 苏伟   

  1. 河北省石家庄平安医院普外科(石家庄 050021)
  • 收稿日期:2019-09-19 发布日期:2020-04-27
  • 通讯作者: 李斌,E-mail:1318934013@qq.com
  • 作者简介:李斌,男,(1981-),本科,主治医师,从事肿瘤外科的研究。

Establishment of a colorectal cancer xenograft model to study the bacterial infection in the intestine of mice and the mechanism of decitabine combined with cisplatin chemotherapy

LI Bin, FENG Baoheng, YIN Fuxia, SU Wei   

  1. Department of General Surgery,Pingan Hospital,Shijiazhuang 050021,China
  • Received:2019-09-19 Published:2020-04-27

摘要: 目的 探讨地西他滨联合顺铂药物治疗结直肠癌的效果以及对肠道菌群结构的影响。方法 本研究构建小鼠结直肠癌移植瘤模型,检测地西他滨、顺铂及地西他滨联合顺铂用药处理后小鼠体内肿瘤体积及总生存期的变化;检测了地西他滨、顺铂及地西他滨联合顺铂用药处理后小鼠移植瘤组织中ABCB1与MYC基因表达量的变化;采集小鼠粪便样本,Miseq测序后比较小鼠模型肠道菌群结构的变化。结果 地西他滨与顺铂联合用药后能够降低小鼠移植瘤模型中肿瘤的生长速率并且延长小鼠的总生存期;联合用药能够降低小鼠模型中ABCB1与MYC基因的表达量;而Miseq测序结果表明不同用药处理后小鼠肠道内的菌群发生了显著变化,结直肠癌移植瘤小鼠模型的粪便中费格森埃希菌、粪肠球菌等致病菌的检出率较高。结论 地西他滨联合顺铂治疗结直肠癌能够有效的抑制肿瘤生长,并且延长总生存期;而小鼠模型肠道内致病菌比例大,可能是影响结直肠疾病发生发展的重要原因;且使用顺铂治疗结直肠癌时还需配合肠道菌群调理药物进行联合治疗。

关键词: 结直肠癌, 菌群, 地西他滨, 顺铂, 联合用药

Abstract: Objective The aim of this study was to investigate the effect of decitabine combined with cisplatin in the treatment of colorectal cancer and its effect on the structure of intestinal flora.Methods In the study,a mouse colorectal cancer xenograft model was established,and the changes in tumor volume and overall survival of mice after the treatment with decitabine,cisplatin,and decitabine combined with cisplatin were measured;the changes of ABCB1 and MYC gene expression in transplanted tumor tissue from mice treated with decitabine,cisplatin,and decitabine combined with cisplatin were detected;fecal samples of mice were collected,the changes of intestinal flora structure were compared in mouse models by Miseq sequencing.Results The combined use of decitabine and cisplatin could reduce the tumor growth rate and prolong the overall survival time of mouse transplanted tumor models;the combined use could reduce the expression of ABCB1 and MYC genes in a model model.The result of Miseq sequencing showed that the intestinal flora of mice changed significantly after different treatments.The detection rates of Escherichia coli,Enterococcus faecalis and other pathogenic bacteria were significantly higher in the stool of colorectal cancer xenograft mouse models.Conclusion Decitabine combined with cisplatin in the treatment of colorectal cancer can effectively inhibit the growth of tumor and prolong the overall survival time.The larger proportion of pathogenic bacteria in the intestinal track of mouse models may be the important reason for the development of colorectal diseases.When using cisplatin to treat colorectal cancer,it also needs to be combined with intestinal flora conditioning drugs for combined treatment.

Key words: Colorectal cancer, Flora, Decitabine, Cisplatin, Drug combination

中图分类号: