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Ming Hong
Guangzhou University of Chinese Medicine
Corresponding Author
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Background Signal transducer and activator of transcription-3 (STAT-3) can facilitate cancer progression and metastasis by being constitutively active via various signalling. 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 patient-derived xenograft 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 signalling pathway.
Results Our research have demonstrated that genipin suppresses STAT-3 phosphorylation and nuclear translocation, which may attribute to the binding capacity of this compound to the Src homology-2 (SH2) domain of STAT-3. In addition, we also demonstrated the therapeutic effects of genipin in patient-derived HCC xenograft mice model.
Conclusion In conclusion, genipin showed therapeutic potential for HCC treatment by interacting with SH2-STAT-3 domain and suppressing the activity of STAT-3. In future study, further research are expected for exploring the potential role of genipin in combination with chemotherapy or radiotherapy for HCC.
Keywords
Hepatocellular carcinoma, Signal transducer and activator of transcription-3, Genipin, Angiogenesis, Cancer invasion
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CURRENT STATUS: Published
View the published article at Journal of Experimental & Clinical Cancer Research.
Version 1
Posted 05 Jun, 2020
No community comments so far
Review #1 received
Received 20 Jun, 2020
Review #2 received
Received 13 Jun, 2020
Reviewer #3 agreed
On 07 Jun, 2020
Reviewer #2 agreed
On 07 Jun, 2020
Reviewer #1 agreed
On 03 Jun, 2020
Editor assigned
On 01 Jun, 2020
Reviewers invited
Invitations sent on 01 Jun, 2020
Submission checks complete
On 31 May, 2020
Editor invited
On 31 May, 2020
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On 30 May, 2020
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Subject Areas
Clinical Pharmacology
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A new preprint design is coming!
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See the published version of this preprint at Journal of Experimental & Clinical Cancer Research.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Ming Hong
Guangzhou University of Chinese Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Experimental & Clinical Cancer Research.
Version 1
Posted 05 Jun, 2020
No community comments so far
Review #1 received
Received 20 Jun, 2020
Review #2 received
Received 13 Jun, 2020
Reviewer #3 agreed
On 07 Jun, 2020
Reviewer #2 agreed
On 07 Jun, 2020
Reviewer #1 agreed
On 03 Jun, 2020
Editor assigned
On 01 Jun, 2020
Reviewers invited
Invitations sent on 01 Jun, 2020
Submission checks complete
On 31 May, 2020
Editor invited
On 31 May, 2020
First submitted
On 30 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Clinical Pharmacology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Experimental & Clinical Cancer Research.
Background Signal transducer and activator of transcription-3 (STAT-3) can facilitate cancer progression and metastasis by being constitutively active via various signalling. 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 patient-derived xenograft 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 signalling pathway.
Results Our research have demonstrated that genipin suppresses STAT-3 phosphorylation and nuclear translocation, which may attribute to the binding capacity of this compound to the Src homology-2 (SH2) domain of STAT-3. In addition, we also demonstrated the therapeutic effects of genipin in patient-derived HCC xenograft mice model.
Conclusion In conclusion, genipin showed therapeutic potential for HCC treatment by interacting with SH2-STAT-3 domain and suppressing the activity of STAT-3. In future study, further research are expected for exploring the potential role of genipin in combination with chemotherapy or radiotherapy for HCC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
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