基于Rab27a研究厚朴三物汤对结直肠癌模型小鼠外泌体的影响
DOI:
作者:
作者单位:

1.河南中医药大学;2.郑州大学第五附属医院;3.河南中医药大学第一附属医院

作者简介:

通讯作者:

中图分类号:

基金项目:

河南省自然科学(222300420489)


To study the effect of Houpu Sanwu decoction on exosomes of colorectal cancer model mice based on Rab27a
Author:
Affiliation:

1.Henan University of Chinese Medicine;2.The Fifth Affiliated Hospital of Zhengzhou University;3.The First Affiliated Hospital of Henan University of Chinese Medicine

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的:探讨厚朴三物汤对C57BL/6J小鼠皮下瘤的影响和机制。方法:将小鼠结直肠癌MC-38细胞通过皮下注射入C57BL/6J小鼠体内建立结直肠癌皮下瘤模型,将造模成功的小鼠按随机化分组为模型对照组、厚朴三物汤低剂量组、厚朴三物汤中剂量组、厚朴三物汤高剂量组、5-氟尿嘧啶组(5-FU组)、联合组(5-氟尿嘧啶+厚朴三物汤中剂量组),每组小鼠各6只。分别给予生理盐水和厚朴三物汤灌胃或生理盐水和5-FU腹腔注射,1次/天,连续24天。干预期间定期检测小鼠精神状态、饮食等一般情况、定期检测小鼠肿瘤体积的变化。取材后,对各组皮下瘤进行称重并采用HE染色观察小鼠皮下瘤病理组织变化;采用透射电子显微镜、Western blot、NTA对结直肠癌组织来源的外泌体进行鉴定;采用RT-qPCR和WB检测肿瘤组织中Rab27a和外泌体标志物CD63、TSG101、ALIX的mRNA和蛋白表达水平。结果:厚朴三物汤可以抑制小鼠肿瘤的生长,厚朴三物汤各剂量组、联合组的肿瘤生长缓慢,均受到不同程度的抑制,其中中药各剂量组以中剂量灌胃抗癌效果最佳,且与5-FU联用(联合组)呈协同作用;厚朴三物汤可以促使肿瘤发生坏死,表现出与5-FU组相同的抗癌作用,剂量越高坏死程度越严重,并且厚朴三物汤与5-FU联用(联合组)呈协同作用;厚朴三物汤可以抑制小鼠Rab27a和外泌体中特异性标志物CD63、ALIX和TSG101的蛋白表达量和mRNA的相对表达量。结论:厚朴三物汤的抗结直肠癌机制可能与Rab27a调控的外泌体分泌减少有关。

    Abstract:

    Objective: TO investigate THE effect and mechanism of Houpu Sanwu Decoction on subcutaneous tumor in C57BL/6J mice. Methods: Mouse colorectal cancer MC-38 cells were subcutaneously injected into C57BL/6J mice to establish a subcutaneous tumor model of colorectal cancer. The mice with successful model were randomly divided into model control group, Houpu Sanwu decoction low-dose group, Houpu Sanwu decoction medium-dose group, Houpu Sanwu decoction high-dose group, 5-fluorouracil group (5-FU group), and combination group (5-fluorouracil + Houpu Sanwu decoction medium-dose group), with 6 mice in each group. The mice were treated with normal saline and Houpu Sanwu decoction by gavage or normal saline and 5-FU by intraperitoneal injection once a day for 24 consecutive days. During the intervention period, the mental state, diet and other general conditions of mice were regularly detected, and the changes in tumor volume of mice were regularly detected. After sampling, the subcutaneous tumors of each group were weighed and the pathological changes of subcutaneous tumors were observed by HE staining Transmission electron microscopy, Western blot and NTA were used to identify the exosomes derived from colorectal cancer tissues. RT-qPCR and WB were used to detect the mRNA and protein expression levels of Rab27a and exosome markers CD63, TSG101, and ALIX in tumor tissues.Results: Houpu Sanwu decoction could inhibit the growth of tumor in mice. The tumor growth was slow in all dose groups of Houpu Sanwu decoction and its combination group, and the tumor growth was inhibited to varying degrees. The anticancer effect of middle dose of traditional Chinese medicine was the best, and the combination group showed synergistic effect with 5-FU. Houpu Sanwu decoction could induce tumor necrosis, showing the same anticancer effect as 5-FU group, and the higher the dose, the more serious the necrosis was. Moreover, Houpu Sanwu decoction combined with 5-FU showed synergistic effect. Houpusanwu decoction can inhibit the protein and mRNA expression of Rab27a and exosome specific markers CD63, ALIX and TSG101 in mice.Conclusion: Houpu Sanwu Decoction inhibits the secretion of exosomes regulated by Rab27a possibly by inhibiting the secretion of exosomes.

    参考文献
    相似文献
    引证文献
引用本文
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2024-04-11
  • 最后修改日期:2024-06-17
  • 录用日期:2024-09-30
  • 在线发布日期:
  • 出版日期:
防诈骗提示!请勿点击不明链接或添加个人微信。编辑部所有邮箱后缀均为@cnilas.org
关闭