中国实验动物学报2026，Vol.34Issue(8)：1146-1156,11.DOI:10.3969/j.issn.1005-4847.2026.08.005
半夏泻心汤对胃癌细胞来源外泌体诱导BMSCs体内致瘤的影响
Effect of Banxia Xiexin decoction on bone marrow mesenchymal stem cell tumorigenicity induced by gastric cancer cell-derived exosomes
摘要
Abstract
Objective To observe the tumorigenicity of bone marrow mesenchymal stem cells(BMSCs)induced by gastric cancer cell-derived exosomes and the effect of Banxia Xiexin decoction treatment.Methods Exosomes were isolated from human gastric cancer NCI-N87 cells,characterized by transmission electron microscopy and Western Blot,and rat BMSCs were passaged and characterized by inverted microscope and immunofluorescence staining.Sixty SPF BALB/c-Nude mice were randomly divided into and control,model,and high-,medium-,low-dose Banxia Xiexin decoction and groups(n=10 per group).The control group was inoculated with normal BMSC suspension(200 μL in axilla);other groups were inoculated with the same dose of BMSC suspension induced by co-culture of exosomes from gastric cancer cells and BMSCs.High-,medium-,low-dose groups were given 1.56,0.78,0.39 g/kg Banxia Xiexin decoction by gavage,respectively,once a day(0.2 mL each time).The positive group was given 0.015 g/kg 5-FU by intraperitoneal injection once every 3 d(0.2 mL each time).The control group received 0.9％sodium chloride solution at an equal volume.Tumor volume was measured every 7 d.After 21 d,subcutaneous tumors were stripped and mass,tumor length and diameter were measured,and tumor volume and inhibition rates were calculated.The tumor tissue ultrastructure was observed by transmission electron microscopy,and latent membrane protein 1(LMP1)and transcription factor 21(TCF21)expression was detected by immunohistochemical staining.Results No tumor formation was observed in the control group after inoculation with normal BMSCs.In the remaining groups,subcutaneous tumors appeared in the axilla on day 14 after inoculation with BMSCs.Compared with the model group,the tumor volumes in the high-and medium-dose Banxia Xiexin decoction groups and the positive group were reduced(P＜0.05).On day 21,the axillary tumor volume in each group increased significantly.Compared with those in the control group,tumor volume and mass in the model group were significantly increased,while those in the positive and high-and medium-dose Banxia Xiexin decoction groups were significantly smaller than those in the model group(P＜0.05);these groups also exhibited tumor inhibition,which was most significant in the high-dose Banxia Xiexin decoction group(P＜0.05).Transmission electron microscopy showed that tumor cells in the control group were densely distributed,with long spindle-and irregular-shaped nuclei.The nuclear membrane was relatively level,and intranuclear euchromatin was abundant,with subcutaneous fibrous tissue between cells.The cells in the model group were arranged closely,with abundant organelles.The nuclei in each dose group of Banxia Xiexin decoction were irregular and damaged to different degrees.Mucus particles in the nuclei were decreased,small,and high-density,especially in the high-dose Banxia Xiexin decoction group.Immunohistochemistry showed that LMP1 protein expression was increased in the tumor tissue of the model group,while TCF21 protein expression was decreased(P＜0.05).After intervention,LMP1 protein expression was decreased in the tumor body tissue of the positive group and each dose group,while that of TCF21 was increased(P＜0.05).LMP1 and TCF21 expression changes were most significant in the high-dose Banxia Xiexin decoction group(P＜0.05).Conclusions BMSCs induced by gastric cancer cell-derived exosomes had tumorigenic properties in vivo.The mechanism involved may be related to increasing LMP1 and reducing TCF21 expression.Banxia Xiexin decoction reduced LMP1 expression and increased that of TCF21 to inhibit BMSC tumorigenesis induced by gastric cancer cell-derived exosomes in vivo.关键词
胃癌细胞来源外泌体/骨髓间充质干细胞/裸鼠成瘤/LMP1/TCF21Key words
gastric cancer cell-derived exosomes/bone marrow mesenchymal stem cells/nude mice tumorigenesis/LMP1/TCF21分类
生物科学引用本文复制引用
张炜,王运琪,刘喜平,施丽娟,朱中博,王庆苗..半夏泻心汤对胃癌细胞来源外泌体诱导BMSCs体内致瘤的影响[J].中国实验动物学报,2026,34(8):1146-1156,11.基金项目
国家自然科学基金(81860813),甘肃省中医药研究中心开发基金项目(zyzx-2024-zx04),甘肃中医药大学中医学一级学科"岐黄英才"导师专项基金项目(ZYXKBD-202412),甘肃省青年科技基金(23JRRA1729).Funded by National Natural Science Foundation of China(81860813),Gansu Provincial Research Center for Traditional Chinese Medicine Development Fund Project(zyzx-2024-zx04),Gansu University of Chinese Medicine,Traditional Chinese Medicine First-Level Discipline"Qihuang Talented Persons"Tutor Special Fund Project(ZYXKBD-202412),Gansu Province Youth Science and Technology Fund(23JRRA1729). （81860813）
