ReferenceID 5305
Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma
Br J Pharmacol
BACKGROUND AND PURPOSE: As a typical hypervascular tumour, hepatocellular carcinoma (HCC) is predominantly grown through angiogenesis. Geniposide is a promising anti-inflammatory compound found in Gardenia jasminoides, b
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 5305
- Evidence Id
- 21895
- Core Evidence Id
- 21895
- Source Reference Id
- 3863
- Herb2 Reference Id
- HBREF004660
- Subject Paper Key
- HBIN027450_32144747
- Pubmed Id
- 32144747
- Doi
- 10.1111/bph.15046
- Paper Title
- Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma
- Paper Abstract
- BACKGROUND AND PURPOSE: As a typical hypervascular tumour, hepatocellular carcinoma (HCC) is predominantly grown through angiogenesis. Geniposide is a promising anti-inflammatory compound found in Gardenia jasminoides, but its effects on the progression of HCC remain untested. EXPERIMENTAL APPROACH: The anti-HCC effects of geniposide was investigated in cellular models and orthotopic HCC mice. Transcriptional regulation of the VEGF promoter was measured by dual-luciferase reporter assay. The anti-angiogenic action of geniposide was measured by tube formation assay. Both surface plasmon resonance techniques and human phospho-kinase array analysis were utilized to validate the relationship between targets of geniposide and hepatocarcinogenesis. KEY RESULTS: Geniposide exhibited significant disruption of HCC proliferation, invasion, angiogenesis and lung metastasis in orthotopic HCC mice. Geniposide inhibited secretion of VEGF by HCC and suppressed the migration of endothelial cells and the formation of intra-tumour blood vessels, without cytotoxicity and independently of the transcription factor HIF-1alpha. Direct inhibition of TLR4 by geniposide led to the shutdown of the TLR4/MyD88 pathway and STAT3/Sp1-dependent VEGF production. However, LPS, an agonist of TLR4, restored STAT3/Sp1-related VEGF production in geniposide-inhibited HCC angiogenesis. CONCLUSION AND IMPLICATIONS: The direct inhibitory effect of geniposide on TLR4/MyD88 activation contributes to the suppression of STAT3/Sp1-dependent VEGF overexpression in HCC angiogenesis and pulmonary metastasis. This action of geniposide was not affected by stabilization of HIF-1alpha. Our study offers a novel anti-VEGF mechanism for the inhibition of HCC.
- Journal
- Br J Pharmacol
- Publish Year
- 2020
- Experiment Subject
- mouse; human
- Experiment Type
- Animal Experiment
- Phenotype Related
- Hypervascular Tumour; Pulmonary Metastasis; Hepatocellular Carcinoma
- Paper Title Cn
- Paper Title En
- Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma
- Bilingual Status
- semi_complete