Inhibitory Effect and Mechanisms of Yupingfeng San on HMGB1-induced Angiogenesis in Liver Cancer via Modulating RAGE/MEK/ERK Signaling Pathway
10.13422/j.cnki.syfjx.20252027
- VernacularTitle:玉屏风散调控RAGE/MEK/ERK信号通路抑制HMGB1诱导下肝癌血管新生的作用和机制
- Author:
Qian XU
1
;
Wenyue HOU
1
;
Shaomei GAO
1
;
Yichao YAN
1
;
Ting ZOU
1
;
Lurong ZHANG
1
Author Information
1. Suzhou Wumen Medical School Key Laboratory of Evaluation and Transformation of Empirical Prescription，Suzhou Hospital of Traditional Chinese Medicine（TCM）Affiliated to Nanjing University of Chinese Medicine，Suzhou 215009，China
- Publication Type:Journal Article
- Keywords:
Yupingfeng San;
angiogenesis;
high-mobility group box protein 1 （HMGB1）;
liver cancer;
receptor for advanced glycation end-products （RAGE）/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(23):1-11
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the inhibitory effects and mechanisms of Yupingfeng San （YPFS） on high-mobility group box protein 1 （HMGB1）-induced angiogenesis in liver cancer. MethodsAn orthotopic liver cancer model was established in 30 C57BL/6 mice. The mice were randomly divided into a model group， YPFS low-， medium-， and high-dose groups （20， 30， 40 g·kg-1， respectively）， a positive control group （sorafenib， 10 mg·kg-1）， and a normal control group. After 14 days of medication， tumor and adjacent tissues were harvested. Tumor inhibition rates were calculated based on tumor weight. Microvascular density was determined via immunohistochemistry. HMGB1 and vascular endothelial growth factor （VEGF） expression levels were determined using immunofluorescence. An HMGB1-induced human umbilical vein endothelial cell （HUVEC） proliferation model was established， and cell proliferation was evaluated by a methylthiazolyldiphenyl-tetrazolium bromide （MTT） assay. HUVECs were randomly divided into a blank group， a model group （HMGB1 800 μg·L-1）， along with YPFS low-， medium-， and high-dose groups （HMGB1 800 μg·L-1 + YPFS 10， 30， 50 g·L-1， respectively）. HUVEC migration ability was evaluated via a scratch assay and a Trans well chamber assay. Tube formation ability was detected by a tube formation assay. Microvascular sprouting ability was evaluated by an aortic ring assay. Furthermore， RAGE/MEK1/2/ERK1/2 pathway-related protein expression in HUVECs was measured using Western blot （WB）. ResultsCompared with the model group， all three doses of YPFS significantly reduced tumor weight in mice with orthotopic liver cancer （P<0.01）， with inhibition rates of 31.49% ± 8.27%， 49.60% ± 3.77%， and 56.81% ± 9.70%， respectively. Also， YPFS significantly decreased microvascular density in tumor and adjacent tissues （P<0.05）， as well as VEGF and HMGB1 expression levels （P<0.01）. Compared with the blank group， HMGB1 promoted HUVEC proliferation， migration， tube formation， and microvascular sprouting in aortic rings （P<0.05）. After YPFS administration， the HMGB1-induced proliferation rate， migration rate， number of tube formations， and microvascular sprouting in aortic rings were significantly reduced compared with the model group （P<0.01）. Additionally， YPFS downregulated receptor for advanced glycation end products （RAGE）， mitogen-activated protein kinase kinase 1/2 （MEK1/2）， phosphorylated MEK1/2 （p-MEK1/2）， extracellular signal-regulated kinase 1/2 （ERK1/2）， and phosphorylated ERK1/2 （p-ERK1/2） protein expression in HMGB1-induced HUVECs （P<0.01）. ConclusionYPFS exerts anti-angiogenic effects against HMGB1 induction by suppressing the RAGE/MEK/ERK signaling pathway， thereby inhibiting liver cancer tumor growth.
