摘要
目的探讨黄芩素脂质体调控Nrf2-HO-1/GPX4信号通路促进铁死亡抑制NSCLC的机制研究。方法将人NSCLC细胞株A549注射于裸鼠右侧腋下建立NSCLC异位瘤模型,并将小鼠分为对照组、黄芩素脂质体组、Nrf2激活剂组(4-OI)及黄芩素脂质体+4-OI组。观察肿瘤体积和重量变化,HE染色观察肿瘤细胞病理学改变;试剂盒检测肿瘤组织中MDA、ROS、GSH/GSSG及Fe^(2+)水平;免疫组化和荧光染色分别检测肿瘤组织中Ki67和ASCL4表达;Western blot检测肿瘤组织Nrf2、HO-1及GPX4蛋白表达水平。结果黄芩素脂质体干预后,小鼠肿瘤体积和重量显著减小,肿瘤细胞坏死增加,MDA、ROS、Fe^(2+)水平显著升高,GSH/GSSG比值显著降低,Ki67表达水平显著降低,ASCL4表达水平显著升高,Nrf2、HO-1及GPX4蛋白表达水平显著降低;4-OI部分抑制或逆转了黄芩素脂质体对上述指标的调控作用。结论黄芩素脂质体可促进肿瘤细胞铁死亡,进而抑制NSCLC进展,其作用机制可能与抑制Nrf2-HO-1/GPX4信号通路激活有关。
Objective To explore the mechanism of baicalein liposome regulating Nrf2-HO-1/GPX4 signaling pathway to promote ferroptosis and inhibit NSCLC.Methods Human NSCLC cell line A549 was injected into the right armpit of nude mice to establish a NSCLC ectopic tumor model,and the mice were divided into control group,baicalein liposome group,Nrf2 inhibitor group(4-OI)and baicalein liposome+4-OI group.The changes of tumor volume and weight were observed,and the cytopathological changes were observed by HE staining.The levels of MDA,ROS,GSH GSSG and Fe^(2+)in tumor tissues were detected by the kit.The expressions of Ki67 and ASCLA in tumor tissues were detected by immunohistochemistry and fluorescence staining.The expressions of Nrf2,HO-1 and GPX4 in tumor tissues were detected by Western blot.Results After baicalein liposome intervention,tumor volume and weight were decreased significantly,tumor cell necrosis was increased,the levels of MDA,ROS,Fe^(2+)were increased significantly,GSH/GSSG ratio was decreased significantly,the expression of Ki67 was decreased significantly,the expression of ASCL4 was increased significantly,the expressionsof Nrf2,HO-1 and GPX4 weredecreased significantly.4-OI partially inhibited or reversed the regulatory effect of baicalein liposomes on the above indexes.Conclusion Baicalein liposomes can promote iron death of tumor cells,and then inhibit the progression of NSCLC,the mechanism of which may be related to the inhibitionof Nrf2-HO-1/GPX4 signaling pathway.
作者
曾健
周学东
刘英
ZENG Jian;ZHOU Xue-dong;LIU Ying(Department of Pharmacy,Chengdu Third People's Hospital,Chengdu 610031;Chengdu Public Health Clinical Medical Center,Chengdu 610066,China)
出处
《解剖科学进展》
2025年第5期602-605,609,共5页
Progress of Anatomical Sciences
基金
四川省自然科学基金(22NSFSC3871)。
