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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Esophageal Cancer | Primary research

Apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer via the Akt/β-catenin pathway

Authors: Bin Wei, Yuanyuan Wang, Jiawei Wang, Xiaomin Cai, Lingyan Xu, Jingjing Wu, Ying Wang, Wen Liu, Yanhong Gu, Wenjie Guo, Qiang Xu

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Esophageal cancer is the sixth leading cause of cancer-related mortality worldwide, which is partially due to limited progress of therapy. Apatinib, an inhibitor of VEGFR2, has a promising antitumor effect on malignancies. However, the underlying mechanism of its antitumor effect on esophageal cancer remains poorly understood.

Materials and methods

Eighteen pairs of frozen esophageal cancer and their para-cancer samples and 25 paraffin specimens from advanced esophageal cancer patients treated with cisplatin-based regimen were collected. The effects of apatinib on cell growth, cell apoptosis, cell cycle and invasion/migration of esophageal cancer cells were assessed. Bioinformatics, luciferase reporter, immunoprecipitation and immunofluorescence assays were conducted for mechanic investigation. Quantitative RT-PCR, western blotting and immunohistochemistry were used to measure the expression of functional genes. Xenograft tumor growth of mice was performed.

Results

We found that VEGFR2 was highly expressed in esophageal cancer and associated with poor efficacy of cisplatin-based treatment. Apatinib displayed profound actions against tumor cell growth of human esophageal cancer via promoting cell apoptosis and cell cycle arrest. Also, apatinib displayed the inhibitory effects on cell migration and invasion. Moreover, apatinib strongly suppressed the growth of esophageal cancer xenografts in mice. The effects of apatinib on esophageal cancer were partially dependent on its block of the VEGFR2/Akt/β-catenin pathway. Specifically, apatinib induced the degradation of β-catenin and decreased its transcriptional activity through Akt/GSK-3β repression. Further in vitro and in vivo studies revealed that low dose apatinib had a synergistic antitumor effect with cisplatin on esophageal cancer.

Conclusion

Our study indicates that apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer by deactivating the Akt/β-catenin pathway. These findings provide a theoretical foundation for using apatinib as an effective therapeutic drug for esophageal cancer.
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Metadata
Title
Apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer via the Akt/β-catenin pathway
Authors
Bin Wei
Yuanyuan Wang
Jiawei Wang
Xiaomin Cai
Lingyan Xu
Jingjing Wu
Ying Wang
Wen Liu
Yanhong Gu
Wenjie Guo
Qiang Xu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01290-z

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