Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway.
10.1016/j.joim.2025.09.002
- Author:
Mao-Feng ZHONG
1
;
Yu-Jun LUO
2
;
Yu-Yu GUO
3
;
Shuang XIANG
2
;
Wan-Fu LIN
4
,
5
Author Information
1. Characteristic Diagnosis and Treatment Technology Research Institution, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Preventive Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
2. Oncology Department of Traditional Chinese Medicine, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai 200043, China.
3. Oncology Department of Traditional Chinese Medicine, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China.
4. Oncology Department of Traditional Chinese Medicine, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; Faculty of Traditional Chinese Medicine, Naval Medical University, Shanghai 200043, China. Electronic address: fubindiyehua@
5. com.
- Publication Type:Journal Article
- Keywords:
Angiogenesis;
Aurora A;
Hepatocellular carcinoma;
Hypoxic microenvironment;
Jiedu Fang
- MeSH:
Carcinoma, Hepatocellular/blood supply*;
Humans;
STAT3 Transcription Factor/metabolism*;
Interleukin-8/metabolism*;
Liver Neoplasms/blood supply*;
Aurora Kinase A/metabolism*;
Neovascularization, Pathologic/drug therapy*;
Animals;
Signal Transduction/drug effects*;
Mice;
Drugs, Chinese Herbal/therapeutic use*;
Cell Line, Tumor;
Mice, Inbred BALB C;
Mice, Nude;
Angiogenesis
- From:
Journal of Integrative Medicine
2025;23(6):683-693
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis.
METHODS:Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels.
RESULTS:In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A.
CONCLUSION:JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
