沃戈宁诱导线粒体亡,并在扩散大B细胞淋巴瘤中与venetoclax协同作用
Ye Lin1, Xia Jiang2, Mengting Zhao3
1Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, China; Department of Pathology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, China.
Toxicology and applied pharmacology
|September 15, 2024
概括
沃贡尼是一种天然的黄类化合物,通过诱导亡,有效地降低了扩散性大B细胞淋巴瘤 (DLBCL) 细胞活力. 它显示作为独立治疗或与venetoclax结合用于DLBCL治疗的承诺.
科学领域:
- 血液学 血液学 血液学
- 药理学 药理学是指药理学的学科.
- 自然产品 自然产品
背景情况:
- 扩散性大B细胞淋巴瘤 (DLBCL) 是一种具有可变预后的侵袭性血液恶性瘤.
- 像R-CHOP这样的当前免疫化学疗法存在局限性,需要新的治疗药物.
- 包括黄类化合物在内的天然化合物因其抗瘤潜力而受到越来越多的关注.
研究的目的:
- 为了研究从Scutellaria baicalensis中获得的黄类物质沃贡尼对DLBCL的治疗效果.
- 阐明在DLBCL细胞中沃贡因细胞毒性背后的机制.
- 评价作为单一疗法和与venetoclax结合使用的沃戈宁的疗效.
主要方法:
- 评估了沃贡因对DLBCL细胞活力和亡诱导的影响.
- 分析了线粒体膜潜力的变化和与亡相关的蛋白质 (BCL-2,MCL-1,BCL-xL).
- 研究了沃贡因对PI3K和MAPK信号通路的影响.
- 在DLBCL细胞中评估了沃贡因与venetoclax的协同作用.
- 在DLBCL异种移植小鼠模型中测试了wogonin的疗效.
主要成果:
- 沃古尼因剂量和时间的依赖性降低了DLBCL细胞活力.
- 细胞毒性是由亡诱导,线粒体功能障碍和抗亡蛋白的降低调节介导的.
- 沃戈宁通过减少关键蛋白质的酸化来抑制PI3K和MAPK通路.
- 与venetoclax的联合治疗显示出对DLBCL细胞的协同性细胞毒性.
- 沃贡尼的使用在体内阻碍了瘤的进展,没有显著的副作用.
结论:
- 沃戈宁通过诱导亡和途径抑制表现出显著的抗DLBCL活性.
- 沃贡因显示出作为DLBCL的新型治疗剂的潜力.
- 在DLBCL治疗中,wogonin可能作为单一疗法或与venetoclax结合有效.
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