文献类型：期刊文献

英文题名：Effect of Guiqi Yiyuan Ointment on Lewis Lung Cancer Mice by Increasing Autophagic Flux and Stabilizing PD-L1 Expression Through Regulation of ERK Signaling Pathway; [归芪益元膏通过调控 ERK 信号通路增加自噬通量稳定 PD-L1 的表达对 Lewis 肺癌小鼠的影响]

作者：Yang N.; Ma Q.; Liang J.; Miao K.; Li S.; Li J.; Li J.

第一作者：Yang N.

机构：[1]School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730101, China;[2]The Key Laboratory of the Ministry of Education of Dunhuang Medicine and Transformation, Lanzhou, 730000, China;[3]Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou, 730101, China

第一机构：甘肃中医药大学

通信机构：[1]School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730101, China|[10735]甘肃中医药大学;

年份：2025

卷号：31

期号：8

起止页码：107

外文期刊名：Chinese Journal of Experimental Traditional Medical Formulae

收录：Scopus(收录号：2-s2.0-105000261153)

语种：英文

外文关键词：autophagy; extracellular regulatory protein kinase（ERK）signaling pathway; Guiqi Yiyuan ointment; lung cancer; programmed cell death ligand-1（PD-L1）

摘要：Objective:To investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase（ERK）signaling pathway. Methods:A Lewis lung cancer mouse model was established. Except for the blank group,the model mice were randomly divided into the model group,Guiqi Yiyuan ointment low,medium,and high dose groups,and the extracellular ERK1/2 inhibitor group,with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75,3.5,7.0 g·kg-1·d-1 for the low,medium,and high dose groups, respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996（100 mg·kg-1·d-1）by gavage. The treatment was administered for 14 consecutive days,after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin（HE）staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1（PD-L1）in tumor tissues. Western blot and real-time quantitative polymerase chain reaction（Real-time PCR）were used to detect the expression of p-ERK1/2,PD-L1,the autophagy marker Beclin-1,the autophagic protein p62, and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. Results:Compared with the model group,the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）,and markedly reduced in the high dose and inhibitor groups（P<0.01）. Tumor cells in all treatment groups became progressively irregular,with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased,and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment（P<0.05）,and significantly reduced in the high dose and inhibitor groups（P<0.01）. The mRNA expression of ERK1/2,PD-L1,Beclin-1,and p62 was reduced in the medium dose group（P<0.05）,while LC3Ⅰ/Ⅱ mRNA expression was elevated（P<0.05）. In the high dose and inhibitor groups,mRNA expression of ERK1/2,PD-L1,Beclin-1,and p62 was significantly reduced（P<0.01）,while LC3Ⅰ/Ⅱ mRNA expression was significantly increased（P<0.01）. Protein expression of p-ERK1/2,PD-L1,Beclin-1,and p62 was reduced in the medium dose group（P<0.05）,and LC3 Ⅰ/Ⅱ protein expression was elevated（P<0.05）. In the high dose and inhibitor groups,protein expression of p-ERK1/2,PD-L1,Beclin-1,and p62 was significantly reduced（P<0.01）,while LC3Ⅰ/Ⅱ protein expression was significantly elevated（P<0.01）. Conclusion: Guiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway,downregulate the expression of p-ERK1/2,promote autophagic flux in tumor cells,and regulate the expression of PD-L1,thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice. ? 2025 China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.