基于JNK/p53通路探讨熊果酸诱导卵巢癌细胞系OVCAR3细胞铁死亡的作用及其机制  

Exploration on Role and Mechanism of Ursolic Acid-Induced Iron Death in Ovarian Cancer Cell Line OVCAR3 Based on JNK/p53 Pathway

作　　者：阮芳[1] 王云飞[1] 王继水[1] RUAN Fang;WANG Yunfei;WANG Jishui(Affiliated Hospital of Jining Medical University,Jining 272000,Shandong,China)

机构地区：[1]济宁医学院附属医院,山东济宁272000

出　　处：《中华中医药学刊》2021年第7期62-64,I0021,共4页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81502255);山东省医学科技发展计划(2017WS336);济宁市科学技术发展规划基金(2014 jnjc09)。

摘　　要：目的基于JNK/p53通路研究熊果酸对卵巢癌细胞系OVCAR3细胞铁死亡的影响及其机制。方法 OVCAR3细胞分别用DMSO(作为对照组)、铁死亡诱导剂、JNK激活剂、熊果酸(UA)、UA+JNK抑制剂干预,检测细胞GSH水平和SOD活性及MDA浓度,同时qPCR检测铁死亡影响因子SLC7A11、GPX4、COX-2、FTH1 mRNA表达,以及JNK/p53通路的表达。结果 UA降低GSH水平、SOD活性,增加MDA浓度,下调SLC7A11、GPX4表达,上调COX-2、FTH1表达,且上调JNK/p53信号表达。UA+JNK抑制剂组中GSH水平、SOD活性、MDA浓度,以及SLC7A11、GPX4、COX-2、FTH1和JNK/p53信号表达无明显差异。结论 UA可通过激活JNK/p53信号通路诱导OVCAR-3细胞铁死亡。Objective To study the effect and mechanism of ursolic acid on ferroptosis of ovarian cancer cell line OVCAR3 based on JNK/p53 pathway. Methods OVCAR3 cells were intervened with DMSO(as a control group), ferroptosis inducer, JNK activator, ursolic acid(UA) and UA+JNK inhibitors to detect the GSH level, SOD activity and MDA concentration of cells, and qPCR was performed to detect relative expressions of ferroptosis-affecting factors including SLC7 A11, GPX4, COX-2 and FTH1 mRNA, as well as JNK/p53 pathway signals. Results UA decreased GSH level and SOD activity, increased MDA concentration, down-regulated the expressions of SLC7 A11 and GPX4, up-regulated the expressions of COX-2 and FTH1, and up-regulated the expression of JNK/p53 signal. There was no significant difference in GSH level, SOD activity, MDA concentration, SLC7 A11, GPX4, COX-2, FTH1 or JNK/p53 signal in the UA+JNK inhibitor group compared with those of the control group. Conclusion UA could induce ferroptosis of OVCAR-3 cells by activating JNK/p53 signaling pathway.

关 键 词：卵巢癌 铁死亡 熊果酸 JNK/p53信号通路 

分 类 号：R285.5[医药卫生—中药学]