中国实验方剂学杂志2026,Vol.32Issue(20):94-101,8.DOI:10.13422/j.cnki.syfjx.20260225
半夏泻心汤通过Akt/c-Myc信号轴对胃癌外泌体诱导骨髓间充质干细胞PD-L1表达的影响
Banxia Xiexintang Affect PD-L1 Expression Induced by Gastric Cancer Cell-derived Exosomes in Bone Marrow Mesenchymal Stem Cells via Akt/c-Myc Signaling Axis
摘要
Abstract
Objective:To observe how Banxia Xiexintang affects programmed cell death 1 ligand 1(PD-L1)expression induced by exosomes derived from gastric cancer cells in bone marrow mesenchymal stem cells(BMSCs)through the protein kinase B(Akt)/c-myelocytomatosis oncogene(c-Myc)signaling axis,and its effects on the migration of BMSCs and gastric cancer cells.Methods:Exosomes were isolated from human gastric cancer NCI-N87 cells and identified by transmission electron microscopy and Western blot.Rat BMSCs were passaged and identified by immunofluorescence staining.A Transwell chamber was used to create a non-contact co-culture system for NCI-N87 exosomes and BMSCs.The experiment was designed with normal,model,Banxia Xiexintang(10%serum containing Banxia Xiexintang),PD-L1 monoclonal antibody(10%blank serum containing PD-L1 antibody),and combination(10%serum containing Banxia Xiexintang and 10%blank serum containing PD-L1 antibody)groups.The suspension of BMSCs was added to the upper chamber of each group,with the normal group receiving serum culture medium without exosomes in the lower chamber,and the model group receiving NCI-N87 exosomes.The Banxia Xiexintang group,PD-L1 monoclonal antibody group,and combination group received 10%serum containing Banxia Xiexintang,10%blank serum containing PD-L1 monoclonal antibody,and 10%serum containing Banxia Xiexintang and 10%blank serum containing PD-L1 antibody,respectively,in the upper chamber.After 96 h,BMSCs from the upper chamber were collected,and the protein levels of p-Akt,Akt,c-Myc,and PD-L1,as well as the mRNA levels of Akt,c-Myc,and PD-L1,were determined by Western blot and Real-time PCR,respectively.The migration of BMSCs and NCI-N87 was assessed by the Transwell method.Results:Compared with the normal group,the model group showed increases in protein levels of p-Akt,c-Myc,and PD-L1,as well as mRNA levels of c-Myc and PD-L1(P<0.05,P<0.01),and no significant change in the protein and mRNA levels of Akt.Compared with the model group,the Banxia Xiexintang group,PD-L1 monoclonal antibody group,and combination group showed decreases in protein levels of p-Akt,c-Myc,and PD-L1(P<0.01).In addition,they had significant effects on the protein and mRNA levels of Akt.The combination group showed greater reductions in the protein and mRNA levels of c-Myc and PD-L1 than the Banxia Xiexintang group and PD-L1 monoclonal antibody group(P<0.05).Compared with the normal group,the model group showed increases in the number of migrating NCI-N87 and BMSCs(P<0.05,P<0.01).Compared with the model group,the Banxia Xiexintang group,PD-L1 monoclonal antibody group,and combination group showed decreases in the number of migrating NCI-N87 and BMSCs(P<0.05,P<0.01),with the combination group showing greater reductions in the number of migrating NCI-N87 and BMSCs than the Banxia Xiexintang group and PD-L1 monoclonal antibody group(P<0.01).Conclusion:Banxia Xiexintang can lower the PD-L1 expression induced by gastric cancer cell-derived exosomes in BMSCs induced and inhibit the migration of BMSCs and gastric cancer cells.Moreover,it has a synergistic effect when being used together with PD-L1,possibly related to the regulation of the Akt/c-Myc signaling axis.关键词
半夏泻心汤/胃癌细胞来源外泌体/骨髓间充质干细胞/蛋白激酶B(Akt)/髓细胞增生原癌基因(c-Myc)信号轴/程序性死亡-配体1(PD-L1)Key words
Banxia Xiexintang/gastric cancer cell-derived exosomes/bone marrow mesenchymal stem cells/protein kinase B(Akt)/c-mycmyelocytomatosis oncogene(c-Myc)signaling axis/programmed cell death 1-ligand 1(PD-L1)分类
医药卫生引用本文复制引用
张炜,刘喜平,施丽娟,朱中博,王庆苗..半夏泻心汤通过Akt/c-Myc信号轴对胃癌外泌体诱导骨髓间充质干细胞PD-L1表达的影响[J].中国实验方剂学杂志,2026,32(20):94-101,8.基金项目
国家自然科学基金项目(81860813) (81860813)