中国中医药信息杂志2024,Vol.31Issue(9):110-116,7.DOI:10.19879/j.cnki.1005-5304.202401230
归芪益元膏联合顺铂调节AMPK/ULK1信号通路对Lewis肺癌荷瘤小鼠肿瘤组织的影响
Effects of Guiqi Yiyuan Ointment Combined with Cisplatin on Regulating the AMPK/ULK1 Signaling Pathway in Tumor Tissue of Lewis Lung Cancer Bearing Mice
摘要
Abstract
Objective To observe the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin in Lewis lung cancer bearing mice based on AMPK/ULK1 signaling pathway.Methods The mice were inoculated with Lewis lung cancer cells to establish a subcutaneous tumor model in the right axillary subcutaneous area,and were randomly divided into blank group,model group,cisplatin group and Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups,with 10 mice in each group.The cisplatin group received intraperitoneal injection of 5 mg/kg(once every 7 days)cisplatin,while the Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups received gavage of 7.0,3.5 and 1.75 g/kg Guiqi Yiyuan Ointment on the basis of cisplatin group,once a day,for 14 consecutive days.HE staining was used to observe the morphology of tumor tissue,immunohistochemical method was used to detect the protein expression of p-AMPK and p-ULK1 in tumor tissue,transmission electron microscopy was used to observe the number of autophagosomes,RT-PCR was used to detect the expression of p62,Beclin-1,Atg5 and LC3 mRNA in tumor tissue,Western blot was used to detect the expression of Beclin-1,p62,Atg5,LC3 and AMPK/ULK1 signaling pathway proteins in tumor tissue.Results Compared with the model group,the tumor mass of mice in all administration groups decreased significantly(P<0.05);the tumor tissue showed patchy necrotic areas and an increase in the number of autophagosomes,the mRNA expressions of Beclin-1,Atg5,and LC3 increased,the protein expressions of Beclin-1,Atg5,LC3 Ⅱ/Ⅰ,AMPK,p-AMPK,ULK1 and p-ULK1 increased,and the expression of p62 mRNA and protein decreased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in Guiqi Yiyuan Ointment high-,medium-dosage+cisplatin groups decreased(P<0.05),the tumor inhibition rate increased;the expressions of ULK1 protein and Atg5 mRNA in tumor tissue of Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups significantly increased(P<0.05),the expressions of Beclin-1 and LC3 mRNA in Guiqi Yiyuan Ointment high-,medium-dosage+cisplatin groups significantly increased(P<0.05),the expressions of Atg5,LC3 Ⅱ/Ⅰ,AMPK,p-AMPK and p-ULK1 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05),the expression of p62 mRNA in Guiqi Yiyuan Ointment high-dosage+cisplatin group significantly decreased(P<0.05),the expression of Beclin-1 protein significantly increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin may activate autophagy and inhibit subcutaneous tumor growth in Lewis lung cancer bearing mice through the AMPK/ULK1 signaling pathway.关键词
肺癌/归芪益元膏/顺铂/细胞自噬/AMPK/ULK1信号通路Key words
lung cancer/Guiqi Yiyuan Ointment/cisplatin/autophagy/AMPK/ULK1 signaling pathway分类
医药卫生引用本文复制引用
李尚,梁建庆,靳银霞,杨楠,薛春霞,李娟,李金田..归芪益元膏联合顺铂调节AMPK/ULK1信号通路对Lewis肺癌荷瘤小鼠肿瘤组织的影响[J].中国中医药信息杂志,2024,31(9):110-116,7.基金项目
国家自然科学基金(82160872) (82160872)
甘肃省教育厅"双一流"科研重点项目(GSSYLXM-05) (GSSYLXM-05)
甘肃省中医药研究中心开放课题(zyzx-2020-zx17) (zyzx-2020-zx17)
2022年度中医学一级学科"岐黄英才"导师专项基金博导项目(ZYXKBD-202202) (ZYXKBD-202202)
2022年度中医学一级学科"岐黄英才"导师专项基金硕导项目(ZYXKSD-202211) (ZYXKSD-202211)
敦煌医学与转化教育部重点实验室开放课题(DHYX22-06) (DHYX22-06)