Therapeutic Potential of CUDC-907 (Fimepinostat) for Hepatocarcinoma Treatment Revealed by Tumor Spheroids-Based Drug Screening
Background: Cancer is the second leading cause of death globally. However, most of the new anti-cancer agents screened by traditional drug screening methods fail in the clinic because of lack of efficacy. Choosing an appropriate in vitro tumor model is crucial for preclinical drug screening. In this...
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Published in | Frontiers in pharmacology Vol. 12; p. 658197 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
29.10.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Background:
Cancer is the second leading cause of death globally. However, most of the new anti-cancer agents screened by traditional drug screening methods fail in the clinic because of lack of efficacy. Choosing an appropriate
in vitro
tumor model is crucial for preclinical drug screening. In this study, we screened anti-hepatocarcinoma (HCC) drugs using a novel spheroid cell culture device.
Methods:
Four HCC cell lines were three-dimensionally (3D) cultured to screen 19 small molecular agents. 3D-cultured primary HCC cells and a tumor-bearing mouse model were used to verify the candidate anti-hepatocarcinoma agent. Cell function experiments and western blotting were conducted to explore the anti-hepatocarcinoma mechanism of the candidate agent.
Results:
We found that CUDC-907 can serve as a potent anti-hepatocarcinoma agent. The study data show that CUDC-907 (fimepinostat), a novel dual acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC), has potent inhibitory effects on HCC cell lines and primary HCC cells
in vitro
, Animal studies have shown that CUDC-907 can also suppress HCC cells
in vivo
. Furthermore, we found that CUDC-907 inhibits the PI3K/AKT/mTOR pathway and downregulates the expression of c-Myc, leading to the suppression of HCC cells.
Conclusion:
Our results suggest that CUDC-907 can be a candidate anti-HCC drug, and the 3D
in vitro
drug screening method based on our novel spheroid culture device is promising for future drug screening efforts. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Federica Barbieri, University of Genoa, Italy Reviewed by: Laia Caja, Uppsala University, Sweden Roberto Würth, German Cancer Research Center (DKFZ), Germany This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology These authors have contributed equally to this work and share first authorship Haishu Lin, Shenzhen Technology University, China |
ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2021.658197 |