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Effect of Angiotensin II on the Malignant Biological Behaviors of Colorectal Cancer Cells and Its Mechanism of Action

Received: 17 May 2023    Accepted: 2 June 2023    Published: 9 June 2023
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Abstract

Objective To explore the effects of angiotensin II (AngII) and the angiotensin II type I receptor (AT1R) antagonist Losartan on the malignant biological behaviors of colorectal cancer (CRC) cells including proliferation, invasion, migration and epithelial-mesenchymal transition (EMT), as well as the underlying mechanism of action. Methods The CRC cell line CT26 was cultured in vitro, and the expression of AT1R in CT26 cells was detected by immunofluorescence staining. Cells were divided into control group, AngII treatment group, and Losartan + AngII treatment group. We analyzed cell growth, proliferation, migration and invasion in the above three groups by adopting functional experiments. Meanwhile, ELISA was performed to detect the expression levels of AngII, TGF-β and TNF-α in cell supernatants, and the Western blotting (WB) assay was carried out to detect the expression of related proteins. In addition, the xenograft tumor nude mouse model was constructed to explore the impact of AT1R antagonist Losartan on the in vivo growth of CRC cells. Results Through experiments in vitro, immunofluorescence staining results verified that AT1R was significantly expressed in CT26 cells. Compared with control group, AngII treatment remarkably promoted the growth, proliferation, migration and invasion of CT26 cells. In the meantime, relative to AngII treatment group, Losartan + AngII treatment group dramatically suppressed the growth, proliferation, migration and invasion of CT26 cells (P < 0.05). Moreover, relative to control group, AngII treatment evidently up-regulated the expression levels of MMP-2, MMP-9, N-cadherin, Vimentin, Snail and p-Smad proteins in cells, and induced the down-regulated expression of E-cadherin protein. Compared with AngII treatment group, Losartan + AngII treatment group showed dramatically decreased expression levels of MMP-2, MMP-9, N-cadherin, Vimentin, Snail and p-Smad proteins in cells, whereas significantly elevated expression of E-cadherin protein (P < 0.05). After AngII treatment, the TGF-β level secreted in cells was higher than that in control group, while that in cells of Losartan + AngII treatment group markedly decreased relative to AngII treatment group (P < 0.05). As revealed by in vivo experimental results, the xenograft tumor growth was evidently suppressed in Losartan + AngII treatment group compared with control group and AngII treatment group, and the serum AngII, TGF-β and TNF-α levels in mice were markedly reduced (P < 0.05). Conclusions AngII promotes the proliferation, migration, invasion and EMT of CT26 cells, while Losartan can antagonize the effect of AngII on promoting malignant growth of CRC both in vivo and in vitro.

Published in Cancer Research Journal (Volume 11, Issue 2)
DOI 10.11648/j.crj.20231102.17
Page(s) 78-85
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Colorectal Cancer, Angiotensin II, Epithelial-mesenchymal Transition

References
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  • APA Style

    Yingxue Yang, Xiaotian Yang, Qinghua Wang. (2023). Effect of Angiotensin II on the Malignant Biological Behaviors of Colorectal Cancer Cells and Its Mechanism of Action. Cancer Research Journal, 11(2), 78-85. https://doi.org/10.11648/j.crj.20231102.17

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    ACS Style

    Yingxue Yang; Xiaotian Yang; Qinghua Wang. Effect of Angiotensin II on the Malignant Biological Behaviors of Colorectal Cancer Cells and Its Mechanism of Action. Cancer Res. J. 2023, 11(2), 78-85. doi: 10.11648/j.crj.20231102.17

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    AMA Style

    Yingxue Yang, Xiaotian Yang, Qinghua Wang. Effect of Angiotensin II on the Malignant Biological Behaviors of Colorectal Cancer Cells and Its Mechanism of Action. Cancer Res J. 2023;11(2):78-85. doi: 10.11648/j.crj.20231102.17

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  • @article{10.11648/j.crj.20231102.17,
      author = {Yingxue Yang and Xiaotian Yang and Qinghua Wang},
      title = {Effect of Angiotensin II on the Malignant Biological Behaviors of Colorectal Cancer Cells and Its Mechanism of Action},
      journal = {Cancer Research Journal},
      volume = {11},
      number = {2},
      pages = {78-85},
      doi = {10.11648/j.crj.20231102.17},
      url = {https://doi.org/10.11648/j.crj.20231102.17},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20231102.17},
      abstract = {Objective To explore the effects of angiotensin II (AngII) and the angiotensin II type I receptor (AT1R) antagonist Losartan on the malignant biological behaviors of colorectal cancer (CRC) cells including proliferation, invasion, migration and epithelial-mesenchymal transition (EMT), as well as the underlying mechanism of action. Methods The CRC cell line CT26 was cultured in vitro, and the expression of AT1R in CT26 cells was detected by immunofluorescence staining. Cells were divided into control group, AngII treatment group, and Losartan + AngII treatment group. We analyzed cell growth, proliferation, migration and invasion in the above three groups by adopting functional experiments. Meanwhile, ELISA was performed to detect the expression levels of AngII, TGF-β and TNF-α in cell supernatants, and the Western blotting (WB) assay was carried out to detect the expression of related proteins. In addition, the xenograft tumor nude mouse model was constructed to explore the impact of AT1R antagonist Losartan on the in vivo growth of CRC cells. Results Through experiments in vitro, immunofluorescence staining results verified that AT1R was significantly expressed in CT26 cells. Compared with control group, AngII treatment remarkably promoted the growth, proliferation, migration and invasion of CT26 cells. In the meantime, relative to AngII treatment group, Losartan + AngII treatment group dramatically suppressed the growth, proliferation, migration and invasion of CT26 cells (P in vivo experimental results, the xenograft tumor growth was evidently suppressed in Losartan + AngII treatment group compared with control group and AngII treatment group, and the serum AngII, TGF-β and TNF-α levels in mice were markedly reduced (P Conclusions AngII promotes the proliferation, migration, invasion and EMT of CT26 cells, while Losartan can antagonize the effect of AngII on promoting malignant growth of CRC both in vivo and in vitro.},
     year = {2023}
    }
    

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  • TY  - JOUR
    T1  - Effect of Angiotensin II on the Malignant Biological Behaviors of Colorectal Cancer Cells and Its Mechanism of Action
    AU  - Yingxue Yang
    AU  - Xiaotian Yang
    AU  - Qinghua Wang
    Y1  - 2023/06/09
    PY  - 2023
    N1  - https://doi.org/10.11648/j.crj.20231102.17
    DO  - 10.11648/j.crj.20231102.17
    T2  - Cancer Research Journal
    JF  - Cancer Research Journal
    JO  - Cancer Research Journal
    SP  - 78
    EP  - 85
    PB  - Science Publishing Group
    SN  - 2330-8214
    UR  - https://doi.org/10.11648/j.crj.20231102.17
    AB  - Objective To explore the effects of angiotensin II (AngII) and the angiotensin II type I receptor (AT1R) antagonist Losartan on the malignant biological behaviors of colorectal cancer (CRC) cells including proliferation, invasion, migration and epithelial-mesenchymal transition (EMT), as well as the underlying mechanism of action. Methods The CRC cell line CT26 was cultured in vitro, and the expression of AT1R in CT26 cells was detected by immunofluorescence staining. Cells were divided into control group, AngII treatment group, and Losartan + AngII treatment group. We analyzed cell growth, proliferation, migration and invasion in the above three groups by adopting functional experiments. Meanwhile, ELISA was performed to detect the expression levels of AngII, TGF-β and TNF-α in cell supernatants, and the Western blotting (WB) assay was carried out to detect the expression of related proteins. In addition, the xenograft tumor nude mouse model was constructed to explore the impact of AT1R antagonist Losartan on the in vivo growth of CRC cells. Results Through experiments in vitro, immunofluorescence staining results verified that AT1R was significantly expressed in CT26 cells. Compared with control group, AngII treatment remarkably promoted the growth, proliferation, migration and invasion of CT26 cells. In the meantime, relative to AngII treatment group, Losartan + AngII treatment group dramatically suppressed the growth, proliferation, migration and invasion of CT26 cells (P in vivo experimental results, the xenograft tumor growth was evidently suppressed in Losartan + AngII treatment group compared with control group and AngII treatment group, and the serum AngII, TGF-β and TNF-α levels in mice were markedly reduced (P Conclusions AngII promotes the proliferation, migration, invasion and EMT of CT26 cells, while Losartan can antagonize the effect of AngII on promoting malignant growth of CRC both in vivo and in vitro.
    VL  - 11
    IS  - 2
    ER  - 

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Author Information
  • Department of Gastroenterology, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China

  • Department of Hematology, Affiliated Huaian Hospital of Xuzhou Medical University, Huaian, China

  • Department of Gastroenterology, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China

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