Effect of <italic style="font-style: italic">Yifei Sanjie Pills</italic> （益肺散结丸） Combined with Cisplatin on Plasma Exosomal miRNAs in Lewis Lung Cancer Tumor-derived Mice

SUN Lingling; QI Xiangjun; LI Yanlong; HU Leihao; LIN Lizhu

doi:10.13288/j.11-2166/r.2024.19.013

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Effect of Yifei Sanjie Pills （益肺散结丸） Combined with Cisplatin on Plasma Exosomal miRNAs in Lewis Lung Cancer Tumor-derived Mice

更新时间：2024-09-26

- Effect of Yifei Sanjie Pills （益肺散结丸） Combined with Cisplatin on Plasma Exosomal miRNAs in Lewis Lung Cancer Tumor-derived Mice
- Journal of Traditional Chinese Medicine Vol. 65, Issue 19, Pages: 2032-2040(2024)
- 作者机构：
  
  1.广州中医药大学第一附属医院，广东省广州市机场路16号，510405
  2.广州中医药大学第一临床医学院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2024.19.013
  CLC：
- Received：28 November 2023，
  
  Revised：2024-07-15，
  
  Published：02 October 2024
- 稿件说明：
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孙玲玲,綦向军,李晏龙等.益肺散结丸联合顺铂对Lewis肺癌瘤源小鼠血浆外泌体微小核糖核酸的影响[J].中医杂志,2024,65(19):2032-2040.

SUN Lingling,QI Xiangjun,LI Yanlong,et al.Effect of Yifei Sanjie Pills （益肺散结丸） Combined with Cisplatin on Plasma Exosomal miRNAs in Lewis Lung Cancer Tumor-derived Mice[J].Journal of Traditional Chinese Medicine,2024,65(19):2032-2040.
孙玲玲,綦向军,李晏龙等.益肺散结丸联合顺铂对Lewis肺癌瘤源小鼠血浆外泌体微小核糖核酸的影响[J].中医杂志,2024,65(19):2032-2040. DOI： 10.13288/j.11-2166/r.2024.19.013.

SUN Lingling,QI Xiangjun,LI Yanlong,et al.Effect of Yifei Sanjie Pills （益肺散结丸） Combined with Cisplatin on Plasma Exosomal miRNAs in Lewis Lung Cancer Tumor-derived Mice[J].Journal of Traditional Chinese Medicine,2024,65(19):2032-2040. DOI： 10.13288/j.11-2166/r.2024.19.013.

摘要

目的

探究益肺散结丸治疗肺癌的抑瘤效果及作用机制。

方法

构建Lewis肺癌瘤源小鼠，并将其分为模型对照组、顺铂组、顺铂+益肺散结低剂量组以及顺铂+益肺散结高剂量组各12只，分别进行相应干预14天，给药第0天、第3天、第7天、第10天、第14天测量瘤体体积，评价瘤体生长情况，第15天留取小鼠血浆、瘤体组织。选取模型对照组、顺铂组、顺铂+益肺散结高剂量组的血浆，提取血浆外泌体，采用二代测序技术检测分析各组间血浆外泌体微小核糖核酸（miRNA）的表达差异，并通过主成分分析、生物功能富集分析、miRNA-靶基因调控网络分析探究益肺散结丸的潜在作用机制。采用实时荧光定量PCR检测肿瘤组织中miRNA-615-3p的表达，利用Kaplan-Meier plotter（kmplot.com）数据库分析miRNA-615-3p与肺癌总生存期的关系。

结果

与模型对照组比较，顺铂组第10天、顺铂+益肺散结低剂量组以及顺铂+益肺散结高剂量组第7天、第10天、第14天肿瘤体积均明显缩小（

＜0.05或

＜0.01）；与顺铂组比较，顺铂+益肺散结低剂量组以及顺铂+益肺散结高剂量组第10天、第14天肿瘤体积均明显缩小（

＜0.05）。miRNA表达谱主成分分析表明，不同干预组间miRNA的表达有明显差异，模型对照组与顺铂组之间共有21个差异表达的miRNA，模型对照组与顺铂+益肺散结高剂量组之间共有50个差异表达的miRNA，顺铂组与顺铂+益肺散结高剂量组之间共有6个差异表达的miRNA。生物功能富集分析表明，差异表达的miRNA主要参与调控与细胞增殖、分化、自噬等生物活动相关的信号通路。miRNA-靶基因调控网络展示了被靶次数前20的基因，其中既包含已被证实的与肺癌相关miRNA及基因，亦存在值得深入挖掘功能的miRNA。与模型对照组比较，顺铂组及顺铂+益肺散结高剂量组瘤体组织中miRNA-615-3p的相对表达量明显下降（

＜0.05或

＜0.01）。miRNA-615-3p的表达水平与肺癌患者的总生存呈负相关（

＜0.05）。

结论

顺铂联合益肺散结丸可有效抑制Lewis肺癌肿瘤增殖，其抑瘤效果与调节多种miRNA，特别是下调miRNA-615-3p的表达有关。

Abstract

Objective

To investigate the tumor inhibition effect and mechanism of

Yifei Sanjie Pills

（益肺散结丸， YSP） on lung cancer.

Methods

Lewis lung cancer tumor-derived mice were established and divided into four groups including model control group， cisplatin group， cisplatin + YSP low-dose group and cisplatin + YSP high-dose group， with 12 mice in each group. The corresponding interventions were given for 14 days. The tumor volume was measured on the 0th， 3rd， 7th， 10th and 14th days of administration to evaluate the tumor growth. The plasma and tumor tissue were collected on the 15th day. Plasma from the model group， the cisplatin group and the cisplatin+YSP high-dose group were selected， and plasma exosomes were extracted； the differences in miRNA expression among the groups were detected and analyzed by second-generation sequencing technology， and the potential mechanism of action of YSP was investigated by principal component analysis， biofunctional enrichment analysis and miRNA-target gene regulatory network analysis. Quantitative real-time PCR was used to detect the expression of miRNA-615-3p in tumor tissues， and the relationship between miRNA-615-3p and overall survival of lung cancer were analyzed using the Kaplan-Meier plotter （kmplot.com） database.

Results

Compared to that of the model control group， the tumor volume of the cisplatin group on day 10， and the cisplatin + YSP low- and high-dose groups on day 7， 10， and 14 were significantly reduced （

＜0.05 or

＜0.01）. Compared to that of the cisplatin group， the tumor volume of the cisplatin + YSP low- and high-dose groups on day 10 and 14 was significantly reduced （

＜0.05）. The principal component analysis of miRNA expression profiles showed significant differences in miRNA expression between different intervention groups. There were 21 differentially expressed miRNAs between the model control group and the c

isplatin group， 50 differentially expressed miRNAs between the model control group and the cisplatin+ YSP high-dose group， and 6 differentially expressed miRNAs between the cisplatin group and the cisplatin+ YSP high-dose group. Biological function enrichment analysis showed that the differentially expressed miRNAs were mainly involved in the regulation of signaling pathways related to cell growth， proliferation， differentiation， autophagy and other biological activities. The miRNA-target gene regulatory network showed the top 20 genes that were targeted， among which there were proven miRNAs and genes related to lung cancer， and miRNAs that needed further investigation. The expression of miRNA-615-3p in tumor tissues decreased significantly in the cisplatin group and cisplatin+YSP high-dose group compared to that of the model group（

＜0.05 or

＜0.01）. The miRNA-615-3p was negatively correlated with the survival prognosis of lung cancer（

＜0.05）.

Conclusion

Cisplatin combined with YSP can effectively inhibit the proliferation of Lewis lung cancer tumors， and the tumor-suppressive effect is related to the regulation of multiple miRNAs， especially the downregulation of miRNA-615-3p expression.

关键词

Keywords

references

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⁰

Effect of Yifei Sanjie Pills （益肺散结丸） Combined with Cisplatin on Plasma Exosomal miRNAs in Lewis Lung Cancer Tumor-derived Mice

DOI：10.13288/j.11-2166/r.2024.19.013

摘要

Abstract

关键词

Keywords

references