Cargando…

Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway

Angiogenetic inhibitors are crucial in tumor therapy, and endogenous angiogenesis inhibitors have attracted considerable attention due to their effectiveness, safety, and multi-targeting ability. Arresten and canstatin, which have anti-angiogenesis effects, are the c-terminal fragments of the α1 and...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Lingyu, Guo, Zitao, Zhang, Ji, Yang, Yuliang, Liu, Chunyu, Zhang, Liang, Gu, Zhenghua, Li, Youran, Ding, Zhongyang, Shi, Guiyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409110/
https://www.ncbi.nlm.nih.gov/pubmed/36012259
http://dx.doi.org/10.3390/ijms23168995
_version_ 1784774770217189376
author Zhu, Lingyu
Guo, Zitao
Zhang, Ji
Yang, Yuliang
Liu, Chunyu
Zhang, Liang
Gu, Zhenghua
Li, Youran
Ding, Zhongyang
Shi, Guiyang
author_facet Zhu, Lingyu
Guo, Zitao
Zhang, Ji
Yang, Yuliang
Liu, Chunyu
Zhang, Liang
Gu, Zhenghua
Li, Youran
Ding, Zhongyang
Shi, Guiyang
author_sort Zhu, Lingyu
collection PubMed
description Angiogenetic inhibitors are crucial in tumor therapy, and endogenous angiogenesis inhibitors have attracted considerable attention due to their effectiveness, safety, and multi-targeting ability. Arresten and canstatin, which have anti-angiogenesis effects, are the c-terminal fragments of the α1 and α2 chains of type IV collagen, respectively. In this study, human arresten and canstatin were recombinantly expressed in Escherichia coli (E. coli), and their effects on the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated. Regarding the cell cycle distribution test and 5-ethynyl-2′-deoxyuridine (EdU) assays, arresten and canstatin could repress the proliferation of HUVECs at a range of concentrations. Transwell assay indicated that the migration of HUVECs was significantly decreased in the presence of arresten and canstatin, while tube formation assays suggested that the total tube length and junction number of HUVECs were significantly inhibited by these two proteins; moreover, they could also reduce the expression of vascular endothelial growth factor (VEGF) and the phosphorylation levels of PI3K and Akt, which indicated that the activation of the 3-kinase/serine/threonine-kinase (PI3K/Akt) signaling pathway was inhibited. These findings may have important implications for the soluble recombinant expression of human arresten and canstatin, and for the related therapy of cancer.
format Online
Article
Text
id pubmed-9409110
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94091102022-08-26 Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway Zhu, Lingyu Guo, Zitao Zhang, Ji Yang, Yuliang Liu, Chunyu Zhang, Liang Gu, Zhenghua Li, Youran Ding, Zhongyang Shi, Guiyang Int J Mol Sci Article Angiogenetic inhibitors are crucial in tumor therapy, and endogenous angiogenesis inhibitors have attracted considerable attention due to their effectiveness, safety, and multi-targeting ability. Arresten and canstatin, which have anti-angiogenesis effects, are the c-terminal fragments of the α1 and α2 chains of type IV collagen, respectively. In this study, human arresten and canstatin were recombinantly expressed in Escherichia coli (E. coli), and their effects on the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated. Regarding the cell cycle distribution test and 5-ethynyl-2′-deoxyuridine (EdU) assays, arresten and canstatin could repress the proliferation of HUVECs at a range of concentrations. Transwell assay indicated that the migration of HUVECs was significantly decreased in the presence of arresten and canstatin, while tube formation assays suggested that the total tube length and junction number of HUVECs were significantly inhibited by these two proteins; moreover, they could also reduce the expression of vascular endothelial growth factor (VEGF) and the phosphorylation levels of PI3K and Akt, which indicated that the activation of the 3-kinase/serine/threonine-kinase (PI3K/Akt) signaling pathway was inhibited. These findings may have important implications for the soluble recombinant expression of human arresten and canstatin, and for the related therapy of cancer. MDPI 2022-08-12 /pmc/articles/PMC9409110/ /pubmed/36012259 http://dx.doi.org/10.3390/ijms23168995 Text en © 2022 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
Zhu, Lingyu
Guo, Zitao
Zhang, Ji
Yang, Yuliang
Liu, Chunyu
Zhang, Liang
Gu, Zhenghua
Li, Youran
Ding, Zhongyang
Shi, Guiyang
Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway
title Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway
title_full Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway
title_fullStr Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway
title_full_unstemmed Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway
title_short Recombinant Human Arresten and Canstatin Inhibit Angiogenic Behaviors of HUVECs via Inhibiting the PI3K/Akt Signaling Pathway
title_sort recombinant human arresten and canstatin inhibit angiogenic behaviors of huvecs via inhibiting the pi3k/akt signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409110/
https://www.ncbi.nlm.nih.gov/pubmed/36012259
http://dx.doi.org/10.3390/ijms23168995
work_keys_str_mv AT zhulingyu recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT guozitao recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT zhangji recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT yangyuliang recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT liuchunyu recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT zhangliang recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT guzhenghua recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT liyouran recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT dingzhongyang recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway
AT shiguiyang recombinanthumanarrestenandcanstatininhibitangiogenicbehaviorsofhuvecsviainhibitingthepi3kaktsignalingpathway