Startseite Lebenswissenschaften Vemurafenib downmodulates aggressiveness mediators of colorectal cancer (CRC): Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B) and Transforming Growth Factor β (TGFβ)
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Vemurafenib downmodulates aggressiveness mediators of colorectal cancer (CRC): Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B) and Transforming Growth Factor β (TGFβ)

  • Helon Guimarães Cordeiro ORCID logo , Alessandra Valéria de Sousa Faria und Carmen Veríssima Ferreira-Halder EMAIL logo
Veröffentlicht/Copyright: 10. August 2020

Abstract

Colorectal Cancer (CRC) therapy confronts challenges as chemoresistance and side effects. Therefore, drugs with antitumor properties that downmodulate aggressiveness mediators are required. Studies have shown the relevance of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B), and Transforming Growth Factor β (TGFβ) in mediating proliferation, chemoresistance, and metastasis. In this study, we aimed to investigate the responsiveness of colorectal cancer lines (HT29 and HCT116) towards Vemurafenib and whether this treatment could modulate these aggressiveness mediators. Cytotoxicity Assays (MTT and Trypan Exclusion Test) were performed to evaluate the viability of HT29 and HCT116 cells treated with Vemurafenib. Western blotting was performed to analyze the amount and/or the activity of mediators (LMWPTP, PTP1B, TGFβ, SMAD3), and the immunoprecipitation was performed to evaluate LMWPTP activity. This study brought up novel aspects of Vemurafenib action in colorectal cancer, which can decrease the activity of protein tyrosine phosphatases (LMWPTP and PTP1B) and the TGFβ pathway, making them important in the CRC aggressiveness. By downmodulating colorectal cancer hallmarks, Vemurafenib appears as an interesting candidate for CRC therapeutic protocols.


Corresponding author: Carmen Veríssima Ferreira-Halder, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Monteiro Lobato Street 255, Campinas, 13083-862, SP, Brazil, E-mail:

Award Identifier / Grant number: 2015/20412-7

Award Identifier / Grant number: 2017/08119-8

Award Identifier / Grant number: 131738/2017-8

Award Identifier / Grant number: 001

Acknowledgments

Authors are grateful for the financial support provided by São Paulo Research Foundation (FAPESP) under the grant (2015/20412-7 and 2017/08119-8), and National Council for Scientific and Technological Development (CNPq) under the grant (131738/2017-8). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. Also to Jordana Maria Azevedo Martins for the English revision.

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Supplementary Material

The online version of this article offers supplementary material https://doi.org/10.1515/hsz-2020-0124.


Received: 2020-02-02
Accepted: 2020-03-17
Published Online: 2020-08-10
Published in Print: 2020-08-27

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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