半夏泻心汤含药肠吸收液通过干预TA-BMSCs中SDF1-CXCR4轴抑制胃癌细胞侵袭迁移OA

Objective:To explore whether the intestinal absorption solution containing Banxia Xiexintang(BXT)can inhibit the invasion and migration of gastric cancer cells by interfering with the stromal cell-derived factor 1(SDF1)-CXC chemokine receptor 4(CXCR4)axis in tumor-associated bone marrow mesenchymal stem cells(TA-BMSCs).Methods:The intestinal absorption solution containing BXT was prepared,and the optimal intervention concentration and duration for MFC cells were determined through the cell counting kit-8(CCK-8)assay.A co-culture system was established comprising TA-BMSCs conditioned medium(TA-BMSCs-CM)and gastric cancer MFC cells.The experiment was conducted with a blank control group,a TA-BMSCs-CM group,an SDF1 inhibitor(LY2510924)group,and intervention groups with varying concentrations(55%,70%,85%)of the intestinal absorption solution containing BXT.Cell proliferation was assessed by the CCK-8 assay.Horizontal and vertical cell migration were evaluated via scratch and Transwell assays,respectively.Cell invasion was examined by a Transwell assay with Matrigel.Cell apoptosis was detected by flow cytometry.The levels of factors such as SDF1,matrix metalloproteinase-9(MMP-9),and vascular endothelial growth factor A(VEGFA),as well as the protein levels of macrophage migration inhibitory factor(MIF),CXCR4,VEGFA,and MMP-9,were quantified by ELISA and Western blot,respectively.Results:The CCK-8 assay results indicated that compared with the 24 h intervention,the 48 h interventions with all concentrations of the intestinal absorption solution containing BXT increased the inhibition rate on MFC cells(P<0.01).The half-maximal inhibitory concentration(IC50)of the intestinal absorption solution containing BXT at the time point of 48 h was 68.51%,and subsequent intervention concentrations were selected as 55%,70%,and 85%.Compared with the TA-BMSCs-CM group,the intestinal absorption solution containing BXT(particularly at concentrations of 70%85%)suppressed the proliferation,migration,and invasion of MFC cells,promoted the cell apoptosis(P<0.05,P<0.01),decreased the levels of SDF1,MMP-9,and VEGFA,and downregulated the protein levels of MIF,CXCR4,VEGFA,and MMP-9(P<0.05,P<0.01).The inhibitory effects of the intestinal absorption solution containing BXT were comparable to or superior to those of the SDF1 inhibitor(P<0.01).Conclusion:The intestinal absorption solution containing BXT can inhibit the invasion and migration of gastric cancer cells by interfering with the SDF1-CXCR4 axis in TA-BMSCs.The underlying mechanism may involve the regulation of the MIF/SDF1/CXCR4 signaling pathway and its downstream effector molecules.