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拜卡莱因向MAPK9,诱导肝细胞癌细胞的亡

Weili Wang^1,2,3, Yuxiao Tang², Xiaobin Zhuo⁴

¹Jiangxi University of Chinese Medicine, Nanchang, China.

Chemical biology & drug design

|September 16, 2024

概括

拜卡莱因是一种天然化合物,通过直接向MAPK9.9,诱导肝细胞癌 (HCC) 的亡. 这一发现为HCC治疗提供了潜在的新疗法策略.

科学领域:

生物化学生物化学
分子生物学分子生物学
在瘤学瘤学.

背景情况:

肝细胞癌 (HCC) 是一个重大的全球健康挑战,有效的治疗选择有限.
自然产品正在越来越多地探索它们在HCC管理中的治疗潜力.
一种黄类化合物贝卡莱因具有抗瘤特性,但其在HCC中的直接分子标仍未确定.

研究的目的:

通过使用DNA编程的亲和力标记方法来识别baicalein的直接结合标.
为了验证已识别的点在baicalein介导肝细胞癌细胞亡中的功能性作用.
阐明贝卡莱因抗HCC活性背后的分子机制.

主要方法:

用DNA编程的亲和度标签被用来识别baicalein的结合伙伴.
使用表面等离子体共振 (SPR) 来量化贝卡莱因与其标之间的结合亲和力.
进行了虚拟对接,以分析绑定站点.
使用MAPK9抑制剂 (SP600125) 进行了功能性测试,以验证其作用机制.

主要成果:

拜卡莱因确定了136个具有约束力的标,其中13个在HCC组织中表达不同.
蛋白质激酶MAP激酶9 (MAPK9) 被确定为 Baicalein 的直接标.
拜卡莱因与MAPK9结合,增强了MAPK9水平和下游亡信号,诱导HCC细胞死亡.
抑制MAPK9阻断了拜卡莱因诱导的亡,证实了目标的作用.

结论:

在肝细胞癌中,MAPK9被确定为 Baicalein 的直接分子标.
拜卡莱因通过MAPK9信号通路诱导HCC细胞的亡.
这一发现为贝卡莱因在HCC治疗中的治疗潜力提供了机制基础.

关键词:

用DNA编程的光亲和度标签在MAPK9上,你会发现MAPK9是什么.灭症 (apoptosis) 是一种死亡的过程.巴伊卡莱因 (Baicalein) 是一种植物.肝细胞癌是肝细胞癌.

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