The Mechanism of Dahuang Zhechong Pill Inhibiting Tumor Angiogenesis in KM Mice Based on the HIF-1α/VEGF Signaling Pathway
Objective To investigate the mechanism by which the Dahuang Zhechong pill inhibits tumor angio-genesis in Kunming(KM)mice,focusing on its effects on tumor inhibition rate,tumor volume,tumor mass,hypoxia-induc-ible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),and tumor microvascular density(MVD).The study aims to explore whether the Dahuang Zhechong pill inhibits tumor angiogenesis and control tumor growth via the HIF-1α/VEGF signaling pathway.Methods H22 human liver cancer cells were injected into KM mice to establish subcuta-neous tumor models.After successful modeling,the mice were randomly divided into six groups:a blank group,a model group,a low-dose Dahuang Zhechong pill group,a medium-dose group,a high-dose group,and a Sorafenib group,with 15 mice in each group.The mice were administered the experimental interventions once daily for two consecutive weeks.The Dahuang Zhechong pill groups and the Sorafenib group were administered corresponding drugs via gavage,while the model group received saline via gavage.After the intervention,the tumors were excised,and their length and width were measured to calculate tumor inhibition rate,tumor volume,and tumor mass,which were recorded.Hematoxylin-eosin(HE)staining was used to observe pathological changes in tumor tissues.Real-time fluorescent quantitative polymerase chain reaction(qPCR)was used to detect the transcription levels of HIF-1α and VEGF mRNA.Western blot(WB)was used to detect the protein expression levels of HIF-1α and VEGF.Immunohistochemistry was employed to detect MVD in tumor tissues.Results The tumor inhibition rates in the low,medium,and high-dose Dahuang Zhechong pill groups were 17.11％,21.73％,and 37.09％,respectively,while the inhibition rate in the Sorafenib group was 46.75％.HE staining showed that the high-dose Dahuang Zhechong pill group led to large areas of necrosis in tumor tissues compared to the model group.qPCR and WB results indicated that all treatment groups significantly reduced the expression levels of HIF-1α and VEGF mRNA and protein in tumor tissues compared to the model group(P＜0.05,P＜0.01).The CD31-MVD results demonstrated a significant reduction in MVD in the high-dose Dahuang Zhechong pill group compared to the model group(P＜0.05),with statistical significance.Conclusion Dahuang Zhechong pill may inhibit tumor angiogenesis and control tumor growth through the HIF-1α/VEGF signaling pathway.
万方数据
维普
