莲心碱通过ROS/JNK途径诱导人胶质瘤U251细胞的凋亡  

Liensinine Induces Apoptosis in Glioma U251 Cells through ROS/JNK Pathway

作　　者：李承科 何琴 罗孝全 冯浩 谯飞 LI Chengke;HE Qin;LUO Xiaoquan;FENG Hao;QIAO Fei(Department of Neurosurgery,Nanchong Hospital of Beijing Anzhen Hospital Affiliated to Capital Medical University(Nanchong Central Hospital),Nanchong,Sichuan,637000,China;Department of Burn Plastic Surgery and Cosmetic Dermatology,Nanchong Hospital of Beijing Anzhen Hospital Affiliated to Capital Medical University(Nanchong Central Hospital),Nanchong,Sichuan,637000,China)

机构地区：[1]首都医科大学附属北京安贞医院南充医院·南充市中心医院神经外科,四川省南充市637000 [2]首都医科大学附属北京安贞医院南充医院·南充市中心医院烧伤整形与皮肤美容外科,四川省南充市637000

出　　处：《医学分子生物学杂志》2025年第2期124-130,共7页Journal of Medical Molecular Biology

基　　金：四川省科技计划项目(No.2023JDRC0091)。

摘　　要：目的探讨莲心碱(liensinine,LI)对人胶质瘤U251细胞的抗肿瘤作用及机制。方法以不同浓度LI处理U251和HEB细胞24/48 h,CCK8、克隆形成实验检测细胞活力,流式细胞术检测细胞凋亡,蛋白质印迹法检测凋亡蛋白(Bax/Bcl-2、cleaved PARP)表达水平。分组为对照、LI、NAC、LI+NAC、SP600125、LI+SP600125,DCFH-DA检测ROS,蛋白质印迹分析p-JNK和cleaved PARP。构建U251移植瘤裸鼠模型,评估LI对肿瘤体积、重量及凋亡标志物的影响。结果LI显著抑制U251增殖,降低U251克隆形成,促进细胞凋亡;LI(80μmol/L)诱导ROS生成和JNK磷酸化,NAC和SP600125可逆转此效应;体内实验显示LI抑制肿瘤生长,降低Ki67阳性细胞,促进凋亡。结论LI通过激活ROS/JNK通路诱导凋亡,选择性抑制U251胶质瘤细胞增殖,且对正常细胞无毒性,具有潜在治疗价值。Objective To investigate the effect of liensinine(LI)on apoptosis of U251 glioma cells and its mechanisms.Methods U251 and HEB cells were treated with different concentrations of LI for 24/48 h,CCK8 assay and colony formation assay were performed to detect cell viability,flow cytometer was performed to detect apoptosis,and the expression levels of apoptotic proteins(Bax/Bcl-2,cleaved PARP)were detected by Western blotting.Cells were divided into 6 groups:control,LI,NAC,LI+NAC,SP600125,LI+SP600125.ROS was detected by DCFH-DA and p-JNK/cleaved PARP by Western blotting.U251 xenograft model was established to evaluate the effect of LI on tumor volume/weight and tumor cell apoptosis.Results LI significantly inhibited the proliferation of U251 cells,decreased the colony formation of U251 cells,and promoted apoptosis.LI(80μmol/L)induced ROS production and JNK phosphorylation,which were reversed by NAC and SP600125.In vivo experiments showed that LI inhibited tumor growth,reduced Ki67 positive cells,and promoted apoptosis.Conclusion LI selectively inhibits U251 via ROS/JNK-mediated apoptosis,demonstrating therapeutic potential for glioma.

关 键 词：胶质瘤 莲心碱 细胞凋亡 自噬 LC3B 

分 类 号：R739.4[医药卫生—肿瘤]