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Published in: Chinese Medicine 1/2022

01-12-2022 | Cholangiocarcinoma | Research

Crowberry inhibits cell proliferation and migration through a molecular mechanism that includes inhibition of DEK and Akt signaling in cholangiocarcinoma

Authors: Xue Wang, Xuebing Zhou, Ludan Zhang, Xin Zhang, Chunyu Yang, Yingshi Piao, Jinhua Zhao, Lili Jin, Guihua Jin, Renbo An, Xiangshan Ren

Published in: Chinese Medicine | Issue 1/2022

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Abstract

Background

Cholangiocarcinoma (CCA) is a rare biliary adenocarcinoma related to poor clinical prognosis. Crowberry is an herbal medicine used to control inflammatory diseases and reestablish antioxidant enzyme activity. Although crowberry shows significant therapeutic efficacy in various tumors and diseases, its anticancer effects and specific molecular mechanisms in CCA are poorly understood.

Aim of the study

This study was conducted to characterize crowberry effects on CCA cells behavior.

Materials and methods

The chemical profiles of crowberry extract was qualitatively analyzed by high-performance liquid chromatography (HPLC) and HPLC–tandem mass spectrometry. MTT, colony formation and EdU assays were performed to measure cell proliferation. The effect of crowberry treatment on CCA cell migration was assessed by wound healing and migration assays. Moreover, Hoechst staining assay and flow cytometry were performed to assess the cell apoptosis rate. Western blotting was used to assess the protein expression levels of key factors associated with apoptosis, the Akt signaling pathway, and the epithelial-mesenchymal transition. A xenograft model was established and immunohistochemical and H&E staining was performed to assess crowberry antitumor effects in vivo.

Results

Crowberry clearly inhibited CCA cells proliferation and migration in a dose-dependent manner and induced apoptosis in vitro. Crowberry inactivated the PI3K/Akt signaling pathway by regulating DEK in vitro and significantly inhibited tumor growth by downregulating the DEK expression in xenograft models.

Conclusion

Crowberry inhibits CCA cells proliferation and migration through a molecular mechanism that includes inhibition of DEK and Akt signaling pathway inhibition in vitro and in vivo.

Graphical Abstract

Appendix
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Literature
3.
30.
go back to reference Hetz C, Vitte PA, Bombrun A, Rostovtseva TK, Montessuit S, Hiver A, Schwarz MK, Churc DJ, Korsmeyer SJ, Martinou JC, Antonsson B. Bax channel inhibitors prevent mitochondrion- mediated apoptosis and protect neurons in a model of global brain ischemia. J Biol Chem. 2005;280(52):42960–70. https://doi.org/10.1074/jbc.M505843200.CrossRefPubMed Hetz C, Vitte PA, Bombrun A, Rostovtseva TK, Montessuit S, Hiver A, Schwarz MK, Churc DJ, Korsmeyer SJ, Martinou JC, Antonsson B. Bax channel inhibitors prevent mitochondrion- mediated apoptosis and protect neurons in a model of global brain ischemia. J Biol Chem. 2005;280(52):42960–70. https://​doi.​org/​10.​1074/​jbc.​M505843200.CrossRefPubMed
47.
50.
go back to reference Yi LS, Zhi GW, Jing ZJ, Yi HP, Li L, Chang X, Hong MP, Liang CL, Guang HY. DEK-targeting aptamer DTA-64 attenuates bronchial EMT-mediated airway remodelling by suppressing TGF-β1/Smad, MAPK and PI3K signalling pathway in asthma. J Cell and Mol Med. 2020;24(23):13739–50. https://doi.org/10.1111/jcmm.15942.CrossRef Yi LS, Zhi GW, Jing ZJ, Yi HP, Li L, Chang X, Hong MP, Liang CL, Guang HY. DEK-targeting aptamer DTA-64 attenuates bronchial EMT-mediated airway remodelling by suppressing TGF-β1/Smad, MAPK and PI3K signalling pathway in asthma. J Cell and Mol Med. 2020;24(23):13739–50. https://​doi.​org/​10.​1111/​jcmm.​15942.CrossRef
Metadata
Title
Crowberry inhibits cell proliferation and migration through a molecular mechanism that includes inhibition of DEK and Akt signaling in cholangiocarcinoma
Authors
Xue Wang
Xuebing Zhou
Ludan Zhang
Xin Zhang
Chunyu Yang
Yingshi Piao
Jinhua Zhao
Lili Jin
Guihua Jin
Renbo An
Xiangshan Ren
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2022
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/s13020-022-00623-6

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