Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma.

British Journal of Pharmacology
Cheng ZhangYibin Feng

Abstract

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. 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. 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-1α. 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 ...Continue Reading

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May 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Noor RahmanHaroon Khan
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Methods Mentioned

BETA
transfection
PCR
protein assay
profiler
antibody array
surface plasmon resonance
biosensor
chip
flow cytometry
nuclear translocation

Key Resources (RRID) Mentioned

Addgene_66128
Addgene_24543
Addgene_24983

Software Mentioned

RStudio
ImageJ
Biacore
R programming
R
GlueGO
CluoGO
DAVID
Cytoscape
SPSS Statistics

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