Application of lemon⁃derived extracellular vesicles in overcoming chemoresistance in ovarian cancer cells

WANG Xinyu; LI Xin

doi:10.14188/j.1671-8852.2025.0074

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Application of lemon⁃derived extracellular vesicles in overcoming chemoresistance in ovarian cancer cells

更新时间：2026-11-05

- Application of lemon⁃derived extracellular vesicles in overcoming chemoresistance in ovarian cancer cells
- Medical Journal of Wuhan University Vol. 46, Issue 9, Pages: 1130-1136(2025)
- 作者机构：
  
  武汉大学人民医院妇科湖北武汉 430060
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2025.0074
  CLC： R711
- Received：23 January 2025，
  
  Published：26 September 2025
- 稿件说明：
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王鑫宇,李新.柠檬来源的胞外囊泡在卵巢癌细胞耐药治疗中的应用[J].武汉大学学报（医学版）,2025,46(09):1130-1136.

WANG Xinyu,LI Xin.Application of lemon⁃derived extracellular vesicles in overcoming chemoresistance in ovarian cancer cells[J].Medical Journal of Wuhan University,2025,46(09):1130-1136.
王鑫宇,李新.柠檬来源的胞外囊泡在卵巢癌细胞耐药治疗中的应用[J].武汉大学学报（医学版）,2025,46(09):1130-1136. DOI： 10.14188/j.1671-8852.2025.0074.

WANG Xinyu,LI Xin.Application of lemon⁃derived extracellular vesicles in overcoming chemoresistance in ovarian cancer cells[J].Medical Journal of Wuhan University,2025,46(09):1130-1136. DOI： 10.14188/j.1671-8852.2025.0074.

摘要

目的

探究柠檬来源的胞外囊泡（LDEVs）对卵巢癌顺铂耐药细胞株的作用机制，以及对巨噬细胞极化的影响，为卵巢癌的药物治疗提供思路。

方法

提取并纯化LDEVs，使用透射电镜及纳米示踪技术对其进行表征；分别以不同浓度将其加入正常卵巢上皮细胞（IOSE⁃80）、卵巢癌细胞（A2780）和卵巢癌顺铂耐药细胞（A2780/DDP）中孵育不同时间段检测细胞活力；检测LDEVs在顺铂耐药株（A2780/DDP）中与不同浓度顺铂合用的效果；流式细胞术检测与顺铂合用后耐药株的凋亡水平；Western Blot检测对药物外排相关蛋白小窝蛋白⁃1（CAV⁃1）的影响；流式细胞术检测巨噬细胞极化水平。

结果

提取的LDEVs呈典型的双层膜结构、粒径集中在100~200 nm；LDEVs对A2780、A2780/DDP、IOSE⁃80三种细胞的抑制效果均呈浓度及时间依赖性；LDEVs与顺铂合用能加强对耐药株的抑制效果及凋亡水平；LDEVs能下调CAV⁃1的表达；LDEVs能促进巨噬细胞的极化。

结论

LDEVs通过下调CAV⁃1的表达，增强对耐药细胞株的抑制作用并提高细胞凋亡水平，同时促进巨噬细胞极化，从而在抗肿瘤免疫调控中发挥潜在协同作用。

Abstract

Objective

To investigate the mechanism of lemon⁃derived extracellular vesicles (LDEVs) in cisplatin（DDP）⁃resistant ovarian cancer cell lines and their impact on macrophage polarization

providing potential insights for drug therapy in ovarian cancer.

Methods

LDEVs were extracted and purified

and characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). LDEVs were incubated with normal ovarian epithelial cells（IOSE⁃80）

ovarian cancer cells（A2780）

and drug⁃resistant ovarian cancer cells（A2780/DDP） at various concentrations for different time points to assess cell viability. The effect of LDEVs in combination with different concentrations of DDP on the DDP⁃resistant cell lines was evaluated. Flow cytometry was used to determine apoptosis levels in drug⁃resistant cells after combination treatment with DDP. Western blot analysis was performed to assess the influence of LDEVs on drug efflux protein Caveolin⁃1（CAV⁃1）. Flow cytometry was also used to analyze macrophage polarization.

Results

The extracted LDEVs exhibited a typical bilayer membrane structure with particle sizes concentrated between 100 and 200 nm. LDEVs showed a concentration⁃ and time⁃dependent inhibitory effect on A2780

A2780/DDP

and IOSE⁃80 cell lines. The combination of LDEVs and DDP enhanced the inhibitory effect and apoptosis levels in the drug⁃resistant cell lines. LDEVs downregulated CAV⁃1 expression. Additionally

LDEVs promoted macrophage polarization.

Conclusion

LDEVs enhance the inhibition and apoptosis of drug⁃resistant cell lines by downregulating the expression of CAV⁃1

while also promoting macrophage polarization.

关键词

Keywords

references

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