当归酮通过PI3K/Akt/mTOR信号通路抑制子宫内膜癌细胞RL95-2自噬  

Angelicone inhibits the autophagy of endometrial cancer cells RL95-2 through PI3K/Akt/mTOR signaling pathway

作　　者：陈西 欧阳紫婷 罗岚[1] 沈艳[1] 宁东红[1] 梁煦 CHEN Xi;OUYANG Ziting;LUO Lan;SHEN Yan;NING Donghong;LIANG Xu(TCM Gynecology,Hunan Maternal and Child Health Hospital,Changsha 410000,Hunan,China)

机构地区：[1]湖南省妇幼保健院中医妇科,湖南长沙410000

出　　处：《中南医学科学杂志》2025年第2期217-220,共4页Medical Science Journal of Central South China

基　　金：湖南省中医药科研计划项目(2021316)。

摘　　要：目的 探讨当归酮抑制子宫内膜癌细胞RL95-2自噬的作用机制。方法 设置不同浓度当归酮(0、2.5、5.0、10.0、20.0μmol/L)作用于RL95-2细胞,筛选最佳作用浓度。细胞实验分为对照组(DMSO培养24 h)、当归酮组(20.0μmol/L当归酮原液培养24 h)、当归酮+胰岛素样生长因子-1(IGF-1)组[20.0μmol/L当归酮和磷脂酰肌醇3激酶(PI3K)激活剂IGF-1共同培养24 h]。采用透射电子显微镜观察自噬体的形成,免疫荧光显微镜检测各组微管相关蛋白1轻链3(LC3)的表达水平。Western blotting检测各组信号通路关键蛋白PI3K-p85、蛋白质丝氨酸/苏氨酸激酶(Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)及其磷酸化蛋白水平。结果 当归酮最佳作用浓度为20.0μmol/L。随着当归酮处理时间的递增,细胞内自噬体数量及LC3针点数逐渐增加(P<0.05),磷酸化(p)-Akt、p-mTOR、PI3K-p85表达水平逐渐降低(P<0.05)。与对照组相比,当归酮组细胞自噬体数量增加,LC3蛋白表达水平升高(P<0.05);与当归酮组相比,当归酮+IGF-1组细胞自噬体数量减少,LC3蛋白表达水平降低(P<0.05)。结论 当归酮可能通过PI3K/Akt/mTOR信号通路抑制人子宫内膜癌细胞RL95-2的自噬。Aim To investigate the mechanism of angelicone in inhibiting autophagy of endometrial cancer cell RL95-2.Methods Different concentrations of angelicone(0,2.5,5.0,10.0,20.0 μmol/L) were applied to RL95-2 cells to screen for the optimal concentration.The cells were divided into the control group(DMSO treated for 24 hours),the angelicone group(20.0 μmol/L angelicone stock solution treated for 24 h),and the angelicone +insulin-like growth factor-1(IGF-1) group [(20.0 μmol/L angelicone and phosphoinositide 3-kinase(PI3K) activator IGF-1 co-treated for 24 h)].Transmission electron microscopy was used to observe the formation of autophagosomes,and immunofluorescence microscopy was used to detect the expression levels of microtubule associated protein 1 light chain 3(LC3) in each group.Western blotting was used to detect the levels of key proteins in various signaling pathways,including PI3K-p85,protein serine/threonine kinase(Akt),mammalian target of rapamycin(mTOR),and their phosphorylated proteins.Results The optimal concentration for screening angelicone was 20.0 μmol/L.With the increasing treatment time of angelicone,the number of autophagosomes and LC3 needle points in cells gradually were increased(P<0.05),while the expression levels of phosphorylated(p)-Akt,p-mTOR,and PI3K-p85 in cells gradually were decreased(P<0.05).Compared with the control group,the angelicone group showed an increase in number of autophagosomes and elevated expression levels of LC3 protein(P<0.05).Compared with the angelicone group,the angelicone+IGF-1 group showed a decrease in number of autophagosomes and a decrease in LC3 protein expression levels(P<0.05).Conclusion Angelicone may inhibit autophagy in human endometrial cancer RL95-2 cells by regulating the PI3K/Akt/mTOR signaling pathway.

关 键 词：当归酮 PI3K/AKT/MTOR 子宫内膜癌 自噬 RL95-2细胞 

分 类 号：R737.33[医药卫生—肿瘤]