北京中医药大学学报2025，Vol.48Issue(10)：1377-1389,13.DOI:10.3969/j.issn.1006-2157.2025.10.007
升麻环氧醇苷联合顺铂调控脂质代谢影响A549细胞增殖与凋亡的机制研究
Mechanism of the effect of cimigenoside combined with cisplatin on lipid metabolism and A549 cell proliferation and apoptosis
摘要
Abstract
Objective To investigate the effect and mechanism of a combination of cimigenoside and cisplatin on the proliferation and apoptosis of lung cancer A549 cells.Methods Selecting A549 and BEAS-2B cell lines as the research objects,the CCK-8 method was employed to detect the cell viability of cimigenoside and cisplatin on A549 cells,as well as the cell viability of cimigenoside on BEAS-2B cells,and calculate the half maximal inhibitory concentration(IC50)and 20%inhibitory concentration(IC20).Follow-up experiments were conducted on A549 cells using a IC20 of cimigenoside and cisplatin.A549 cells were divided into control,cisplatin(5.09 μmol/L),cimigenoside(4.39 μmol/L),and cisplatin+cimigenoside groups(5.09 μmol/L+4.39 μmol/L).The four groups were treated with the corresponding drugs for 48 h.The EdU-488 fluorescent probe method was used to detect the positive cell rate of A549 cells,and Annexin V/PI staining was used to detect the apoptosis status of A549 cells.Bodipy 493/503 staining was used to observe lipid droplet formation in A549 cells.Western blotting was used to detect protein kinase B(Akt),phosphorylated Akt(p-Akt),mammalian target of rapamycin(mTOR),steroid regulatory element-binding protein 1(SREBP1),fatty acid synthase(FASN),acetyl CoA carboxylase 1(ACC1),adenosine triphosphate citrate lyase(ACLY),Cyclin E1,cyclin-dependent kinase 2(CDK2),B-cell lymphoma 2(Bcl-2),Bcl-2 related X protein(Bax),and Cleaved-Caspase-3 protein expression in A549 cells.Confocal immunofluorescence was used to detect the average fluorescence intensity of SREBP1 in A549 cells.Results The IC50 and IC20 values of cimigenoside on A549 cells were 22.80±0.93 μmol/L and 4.39±0.73 μmol/L,respectively.The IC50 and IC20 values of cisplatin on A549 cells were 31.57±1.53 μmol/L and 5.09±0.78 μmol/L,respectively.The IC50 of cimigenoside for BEAS-2B cells was 26.60±1.41 μmol/L.Compared with the control group,the EdU-positive cell rate decreased,the cell necrosis rate and total apoptosis rate increased,lipid droplet formation reduced,p-Akt,mTOR,SREBP1,FASN,ACC1,ACLY,Cyclin E1,CDK2,and Bcl-2 protein expression decreased,Bax and Cleaved-Caspase-3 protein expression increased,and the average SREBP1 fluorescence intensity decreased(P<0.05)in the cisplatin,cimigenoside,and cisplatin+cimigenoside groups.Compared with the cisplatin group,the cell necrosis rate increased,and lipid droplet formation was reduced,and SREBP1,Cyclin E1,Bax,and Cleaved-Caspase-3 protein expression decreased,whereas CDK2 and Bcl-2 protein expression increased in the cimigenoside group(P<0.05).The cisplatin+cimigenoside group showed a decrease in cell necrosis rate,an increase in total apoptosis rate,a reduction in lipid droplet formation,a decrease in p-Akt,mTOR,SREBP1,FASN,ACC1,ACLY,Cyclin E1,CDK2,and Bcl-2 protein expression,an increase in Bax and Cleaved-Caspase-3 protein expression,and a decrease in the average fluorescence intensity of SREBP1(P<0.05).Compared with the cimigenoside group,the cisplatin+cimigenoside group showed a decrease in cell necrosis rate,an increase in total apoptosis rate,a reduction in lipid droplet formation,a decrease in p-Akt,mTOR,SREBP1,FASN,ACC1,ACLY,Cyclin E1,CDK2,and Bcl-2 protein expression,an increase in Bax and Cleaved-Caspase-3 protein expression,and a decrease in the average fluorescence intensity of SREBP1(P<0.05).Conclusion The combination of cisplatin and cimigenoside can inhibit the phosphoinositide 3-kinase/Akt/mTOR signaling pathway,regulate SREBP1 expression,and affect the lipid metabolism pathway of A549 cells,thereby inhibiting their proliferation.关键词
升麻环氧醇苷/固醇调节元件结合蛋白1/磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路/肺腺癌细胞Key words
cimigenoside/sterol regulatory element-binding protein 1/phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathway/lung adenocarcinoma cell分类
临床医学引用本文复制引用
李贺,刘文俊,王淳..升麻环氧醇苷联合顺铂调控脂质代谢影响A549细胞增殖与凋亡的机制研究[J].北京中医药大学学报,2025,48(10):1377-1389,13.基金项目
国家自然科学基金项目(No.82174254) （No.82174254）
辽宁省科技计划联合项目(No.2023JH2/101700210) （No.2023JH2/101700210）
辽宁省教育厅科技创新团队项目(No.LJ222510162018) （No.LJ222510162018）
辽宁中医药大学中医药科技创新多学科交叉团队项目(No.2025-Dxkjc-15-02) （No.2025-Dxkjc-15-02）
辽宁中医药大学中西医结合学院"岐济"人才支撑计划项目(No.2023QJ01001) National Natural Science Foundation of China(No.82174254) （No.2023QJ01001）
