囊泡传输的多药性耐药性作为天然化合物的潜在治疗标
Salvatrice Rigogliuso1, Alessandra Cusimano1, Lucia Condorelli1
1Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.
Pharmaceuticals (Basel, Switzerland)
|October 26, 2024
概括
多抗药性癌细胞释放携带P-糖蛋白 (P-gp) 的细胞外囊泡 (EV),促进药物耐药性. 天然化合物可以阻止这种EV转移,可能会逆转癌细胞的抵抗力.
科学领域:
- 癌症生物学 癌症生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞外囊泡 (EVs) 在各种条件下调解细胞间通信.
- 来自多药耐药 (MDR) 癌细胞的EV可以转移P-糖蛋白 (P-gp),使受体细胞产生耐药性.
- 这种通过EV的P-gp水平转移有助于MDR表型的传播.
研究的目的:
- 从MDR癌症模型 (MCF-7R和HL-60R) 中分离和描述EV.
- 研究P-gp在EV中调解药物耐药性的作用.
- 为了确定可以抑制EV释放和P-gp转移的天然化合物.
主要方法:
- 通过纳米粒子追踪分析 (NTA) 和西式斑点检测CD63,HSP70和Syntenin等标记物,将EVs分离和表征.
- 通过Westernblotting和功能测试证实了P-glycoprotein (P-gp) 的存在和通过EVs的转移.
- 在EV治疗和暴露于多克索鲁比后,使用MTS测定来评估药物敏感性.
主要成果:
- 与敏感细胞不同的是,MDR细胞系 (MCF-7R,HL-60R) 释放了带有P-gp的EVs.
- 受体敏感细胞在从EVs中加入P-gp时获得了多克索鲁比辛耐药性.
- 自然化合物 (黄素,卢皮醇,赫普塔科桑) 抑制了EV转移并恢复了药物敏感性.
结论:
- EVs在P-gp的水平转移中发挥着重要作用,在癌症中驱动多药性耐药性.
- 自然化合物显示出作为治疗剂的潜力,可以阻止EV介导的耐药性.
- 针对EV释放和P-gp转移提供了一种针对抗性癌症表型的新策略.
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