海南医科大学学报2025，Vol.31Issue(5)：343-350,8.DOI:10.13210/j.cnki.jhmu.20240731.001
左金丸通过抑制ERK、p38和AKT信号通路抑制肿瘤血管生成和结肠癌生长
ZuoJin Wan inhibits tumor angiogenesis and colorectal cancer growth by suppressing ERK,p38 and AKT signaling pathways
摘要
Abstract
Objective:To investigate the inhibitory effect of Zuojin Wan(ZJW)on tumor angiogenesis by suppressing the ERK1/2,p38MAPK,and AKT signaling pathways.Methods:HUVEC and Lovo cells were treated with ZJW at various concen-trations with or without VEGF.The CCK-8 assay was employed to assess the effect of ZJW on the proliferation of HUVEC and Lovo cells.Flow cytometry was used to observe the effect of different concentrations of ZJW on apoptosis in HUVEC cells.Miga-ration assay,Transwell assay,and tube formation assay were conducted to evaluate the migration,invasion,and tube-forming ability of HUVECs treated with ZJW.A nude mouse subcutaneous xenograft model of human colon cancer Lovo cells was estab-lished,divided into 5 groups:the control group(0.9%saline),low,medium,and high-dose ZJW groups(1 027.5 mg/kg,2 055 mg/kg,4 110 mg/kg),and chemotherapy drug 5-Fu group(50 mg/kg),all administered every other day.On the 21st day of treatment,mice were euthanized,and tumor volumes and weights were compared among groups.Immunohistochemistry was used to detect CD34 expression(microvessel density)in tumor tissues of each group.Western blot analysis was performed to investi-gate the regulatory effects of ZJW on VEGFR2 and its downstream signaling pathways.Results:ZJW inhibited the proliferation of HUVEC and Lovo cells,with a more pronounced inhibitory effect on VEGF-induced HUVEC cell proliferation(P<0.05).ZJW inhibited cell migration,invasion,and tube formation(P<0.05).ZJW suppressed the volume and weight of xenograft tumors in a dose-dependent manner(P<0.05).Compared to the control group,microvessel density in the low,medium,and high-dose ZJW groups showed a dose-dependent decrease(P<0.05).ZJW inhibited the phosphorylation levels of ERK1/2,p38MAPK,and AKT in VEGF-induced HUVEC cells in a dose-and time-dependent manner but had no effect on VEGFR2 phosphorylation ex-pression.Conclusion:ZJW could inhibit tumor angiogenesis,and its mechanism may be associated with the inhibition of the ERK1/2,p38MAPK,and AKT signaling pathways.关键词
左金丸/肿瘤血管生成/结肠癌/ERK1/2/AKT/p38MAPKKey words
Zuojin Wan/Tumor angiogenesis/Colorectal cancer/ERK1/2/AKT/p38MAPK分类
中医学引用本文复制引用
袁杰,孟娇,闫化茹,常彬,孙明瑜,梁婷玉,王子元..左金丸通过抑制ERK、p38和AKT信号通路抑制肿瘤血管生成和结肠癌生长[J].海南医科大学学报,2025,31(5):343-350,8.基金项目
This study was supported by National Natural Science Foundation of China(82374188,82303207),Four Bright Youth Fund of Shuguang Hospital(SGKJ-202115) 国家自然科学基金资助项目(82374188、82303207) （82374188,82303207）
曙光医院四明青年基金(SGKJ-202115) （SGKJ-202115）
