抑制CCK受体可以减少胰腺瘤纤维化,并促进纳米粒子的输送
Thomas Abraham1, Michael Armold2, Christopher McGovern2
1Department of Neural and Behavioral Sciences, Penn State College of Medicine, P.O. Box 850, Hershey, PA 17036, USA.
Biomedicines
|May 25, 2024
概括
作为CCKR抗体的proglumide可以减少胰腺瘤纤维化,从而改善纳米粒子的输送. 这种药物使瘤微环境正常化,增强胰腺管道腺癌 (PDAC) 患者的治疗潜力.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 纳米医学是一种纳米医学.
背景情况:
- 胰腺管道腺癌 (PDAC) 由于其纤维性瘤微环境 (TME) 的原因,预后不佳.
- 瘤纤维化阻碍了治疗药物的输送,包括纳米粒子 (NP).
- 胆囊托基宁受体 (CCKR) 抗剂,如普格胺,已经显示出降低纤维化的潜力.
研究的目的:
- 为了研究proglumide如何减少PDAC TME中的纤维化.
- 为了确定由proglumide诱导的纤维化减少对纳米粒子吸收的影响.
- 探索CCK2受体在PDAC脱细胞中的瘤细胞中的作用.
主要方法:
- 在小鼠中注射PDAC细胞,然后进行proglumide治疗.
- 瘤的ex vivo分析用于纤维化,血管性,星状细胞激活和纳米粒子分布.
- 评估CCK2受体对PANC-1细胞中的原减少的淘汰效应.
主要成果:
- 普罗格卢米德治疗显著降低 stromal 原蛋白和降低癌症相关纤维细胞 (CAF) 激活.
- 普洛胺增加了瘤血管性,并增强了纳米颗粒的瘤内分布.
- 瘤细胞中CCK2受体的淘汰进一步减少了原蛋白,证实了它们在脱质形成中的作用.
结论:
- 通过proglumide阻断CCK2受体,在PDAC TME内产生抗纤维效应.
- 减少纤维化改善了纳米粒子的传递,提供了一种提高PDAC治疗的策略.
- 普罗格胺显示出作为一种辅助疗法的潜力,可以改善胰腺癌中纳米封装治疗的治疗效果.
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