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Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer

Background: Prostate cancer (PCa) is the leading cause of death in men and has poor therapeutic outcomes. Methods: A novel endostatin 33 peptide was synthesized by adding a specific QRD sequence on the basis of the endostatin 30 peptide (PEP06) with antitumor activity. Then, bioinformatic analysis a...

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Autores principales: Liu, Yang, Wang, Chang-Lin, Pang, Zhong-Qi, Gao, Ke, Shen, Lin-Kun, Xu, Wan-Hai, Ren, Ming-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003382/
https://www.ncbi.nlm.nih.gov/pubmed/36902648
http://dx.doi.org/10.3390/jcm12051861
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author Liu, Yang
Wang, Chang-Lin
Pang, Zhong-Qi
Gao, Ke
Shen, Lin-Kun
Xu, Wan-Hai
Ren, Ming-Hua
author_facet Liu, Yang
Wang, Chang-Lin
Pang, Zhong-Qi
Gao, Ke
Shen, Lin-Kun
Xu, Wan-Hai
Ren, Ming-Hua
author_sort Liu, Yang
collection PubMed
description Background: Prostate cancer (PCa) is the leading cause of death in men and has poor therapeutic outcomes. Methods: A novel endostatin 33 peptide was synthesized by adding a specific QRD sequence on the basis of the endostatin 30 peptide (PEP06) with antitumor activity. Then, bioinformatic analysis and subsequent experiments were performed to validate the antitumor function of this endostatin 33 peptide. Results: We found that the 33 polypeptides significantly inhibited growth, invasion and metastasis and promoted the apoptosis of PCa in vivo or vitro, which is more significant than PEP06 under the same conditions. According to 489 cases from the TCGA data portal, the α6β1 high expression group was closely associated with the poor prognosis (Gleason score, pathological N stage, etc.) of PCa and was mainly enriched in the PI3K-Akt pathway. Subsequently, we demonstrated that endostatin 33 peptide can down-regulate the PI3K-Akt pathway via the targeted inhibition of α6β1, thereby inhibiting the epithelial–mesenchymal transition and matrix metalloproteinase in C42 cell lines. Conclusion: The endostatin 33 peptide can exert antitumor effects by inhibiting the PI3K-Akt pathway, especially in tumors with a high expression of the integrin α6β1 subtype, such as prostate cancer. Therefore, our study will provide a new method and theoretical basis for the treatment of prostate cancer.
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spelling pubmed-100033822023-03-11 Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer Liu, Yang Wang, Chang-Lin Pang, Zhong-Qi Gao, Ke Shen, Lin-Kun Xu, Wan-Hai Ren, Ming-Hua J Clin Med Article Background: Prostate cancer (PCa) is the leading cause of death in men and has poor therapeutic outcomes. Methods: A novel endostatin 33 peptide was synthesized by adding a specific QRD sequence on the basis of the endostatin 30 peptide (PEP06) with antitumor activity. Then, bioinformatic analysis and subsequent experiments were performed to validate the antitumor function of this endostatin 33 peptide. Results: We found that the 33 polypeptides significantly inhibited growth, invasion and metastasis and promoted the apoptosis of PCa in vivo or vitro, which is more significant than PEP06 under the same conditions. According to 489 cases from the TCGA data portal, the α6β1 high expression group was closely associated with the poor prognosis (Gleason score, pathological N stage, etc.) of PCa and was mainly enriched in the PI3K-Akt pathway. Subsequently, we demonstrated that endostatin 33 peptide can down-regulate the PI3K-Akt pathway via the targeted inhibition of α6β1, thereby inhibiting the epithelial–mesenchymal transition and matrix metalloproteinase in C42 cell lines. Conclusion: The endostatin 33 peptide can exert antitumor effects by inhibiting the PI3K-Akt pathway, especially in tumors with a high expression of the integrin α6β1 subtype, such as prostate cancer. Therefore, our study will provide a new method and theoretical basis for the treatment of prostate cancer. MDPI 2023-02-27 /pmc/articles/PMC10003382/ /pubmed/36902648 http://dx.doi.org/10.3390/jcm12051861 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Yang
Wang, Chang-Lin
Pang, Zhong-Qi
Gao, Ke
Shen, Lin-Kun
Xu, Wan-Hai
Ren, Ming-Hua
Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer
title Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer
title_full Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer
title_fullStr Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer
title_full_unstemmed Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer
title_short Endostatin 33 Peptide Is a Deintegrin α6β1 Agent That Exerts Antitumor Activity by Inhibiting the PI3K-Akt Signaling Pathway in Prostate Cancer
title_sort endostatin 33 peptide is a deintegrin α6β1 agent that exerts antitumor activity by inhibiting the pi3k-akt signaling pathway in prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003382/
https://www.ncbi.nlm.nih.gov/pubmed/36902648
http://dx.doi.org/10.3390/jcm12051861
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