和厚朴酚通过YAP元件诱导卵巢癌细胞铁死亡的机制  

The mechanism of ferroptosis induction in ovarian cancer cells by honokiol via YAP elements

作　　者：刘芳 张玉芳 夏昕懿 韩菁 周佳燕 Liu Fang

机构地区：[1]嘉兴大学附属第二医院,314000

出　　处：《浙江临床医学》2025年第1期16-19,共4页Zhejiang Clinical Medical Journal

基　　金：浙江省医药卫生科技计划项目(2023KY1210)。

摘　　要：目的 探讨和厚朴酚(HNK)通过Yes相关蛋白(YAP)元件诱导卵巢癌(OC)细胞铁死亡的机制。方法 采用人OC细胞株OVCA420,按不同处理分为对照组(Control组)、HNK组、HNK+铁死亡抑制剂组、HNK+铁死亡激动剂组。比较各组细胞增殖活力、死亡率、迁移与侵袭能力、ROS活性及p-YAP1、YAP1、p-TAZ1、TAZ1、GPX4、ACSL4和TFRC蛋白表达水平,按照试剂盒测定铁死亡标志物MDA和SOD水平,并使用YAP-TEAD抑制剂Peptide 17验证YAP是否是HNK调节铁死亡的关键靶点之一。结果 Control组和HNK组OVCA420细胞迁移率、侵袭率、增殖率、SOD、ROS和MDA水平以及ACSL4、TFRC和GPX4蛋白表达水平比较,差异有统计学意义(P<0.05)。与HNK组比较,铁死亡抑制剂可抑制HNK的作用,铁死亡激动剂促进HNK的作用(P<0.05)。Peptide 17阻断YAP-TEAD信号通路可抑制HNK对铁死亡的调节作用(P<0.05)。结论 HNK可以通过YAP元件诱导OVCA420细胞铁死亡,为OC的抗肿瘤活性提供新的线索和理论支持。Objective To investigate the mechanism by which honokiol(HNK) induces ferroptosis in ovarian cancer(OC) cells through the Yesassociated protein(YAP) pathway. Methods Human OC cell line OVCA420 was employed and divided into various groups: control group, HNK group,HNK + ferroptosis inhibitor group, and HNK + ferroptosis agonist group. Cell proliferation activity, mortality rate, migration and invasion capabilities, ROS activity, and the expression levels of p-YAP1, YAP1, p-TAZ1, TAZ1, GPX4, ACSL4, and TFRC proteins were compared among the groups. Levels of ferroptosis markers MDA and SOD were determined using assay kits, and the YAP-TEAD inhibitor Peptide 17 was used to verify whether YAP is one of the key targets of HNK in regulating ferroptosis. Results The migration rate, invasion rate, proliferation rate, SOD, ROS, MDA levels, as well as ACSL4,TFRC, and GPX4 protein expression levels of OVCA420 cells in the Control group and HNK group showed statistically significant differences(P<0.05).Compared with the HNK group, iron death inhibitors can inhibit the effect of HNK, while iron death agonists promote the effect of HNK(P<0.05). Peptide 17 blocking the YAP-TEAD signaling pathway can inhibit the regulatory effect of HNK on ferroptosis(P<0.05). Conclusion HNK can induce ferroptosis in OVCA420 cells through YAP elements, providing new clues and theoretical support for the anti-tumor activity of OC tumors.

关 键 词：卵巢癌 OVCA420细胞 铁死亡 YAP元件 

分 类 号：R73[医药卫生—肿瘤]