ReferenceID 5299

Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3

J Exp Clin Cancer Res

BACKGROUND: The signal transducer and activator of transcription-3 (STAT-3) can facilitate cancer progression and metastasis by being constitutively active via various signaling. Abundant evidence has indicated that STAT

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Reference Id
5299
Evidence Id
21889
Core Evidence Id
21889
Source Reference Id
3856
Herb2 Reference Id
HBREF004653
Subject Paper Key
HBIN027445_32741371
Pubmed Id
32741371
Doi
10.1186/s13046-020-01654-3
Paper Title
Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3
Paper Abstract
BACKGROUND: The signal transducer and activator of transcription-3 (STAT-3) can facilitate cancer progression and metastasis by being constitutively active via various signaling. Abundant evidence has indicated that STAT-3 may be a promising molecular target for cancer treatment. METHODS: In this study, a dual-luciferase assay-based screening of 537 compounds for STAT-3 inhibitors of hepatocellular carcinoma (HCC) cells was conducted, leading to the identification of genipin. Effects of genipin on HCC were assessed in a patient-derived xenograft nude mice model. Western blotting assay, chromatin immunoprecipitation (ChIP) assay, molecular docking study, tube formation assay, three-dimensional top culture assay, histological examination, and immunofluorescence were utilized to evaluate the regulatory signaling pathway. RESULTS: Our research demonstrated that genipin suppresses STAT-3 phosphorylation and nuclear translocation, which may be attributed to the binding capacity of this compound to the Src homology-2 (SH2) domain of STAT-3. In addition, the therapeutic effects of genipin in a patient-derived HCC xenograft nude mice model were also demonstrated. CONCLUSIONS: In conclusion, genipin showed therapeutic potential for HCC treatment by interacting with the SH2-STAT-3 domain and suppressing the activity of STAT-3. In the future, further research is planned to explore the potential role of genipin in combination with chemotherapy or radiotherapy for HCC.
Journal
J Exp Clin Cancer Res
Publish Year
2020
Experiment Subject
mouse; patient
Experiment Type
Animal & Cell Experiment
Phenotype Related
Cancer; Hepatocellular Carcinoma
Paper Title Cn
Paper Title En
Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3
Bilingual Status
semi_complete