Glipizide Combined with ANP Suppresses Breast Cancer Growth and Metastasis by Inhibiting Angiogenesis through VEGF/VEGFR2 Signaling.
Angiogenesis Inhibitors
/ pharmacology
Animals
Atrial Natriuretic Factor
/ pharmacology
Breast Neoplasms
/ drug therapy
Cell Movement
Cell Proliferation
Diabetes Mellitus, Type 2
/ drug therapy
Female
Glipizide
/ pharmacology
Human Umbilical Vein Endothelial Cells
Humans
Mice
Neovascularization, Pathologic
/ drug therapy
Vascular Endothelial Growth Factor A
/ metabolism
Vascular Endothelial Growth Factor Receptor-2
ANP
Glipizide
HUVECs
breast cancer
metastasis
tumor angiogenesis
tumor growth
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2022
2022
Historique:
received:
17
02
2021
revised:
17
07
2021
accepted:
26
07
2021
pubmed:
14
9
2021
medline:
18
5
2022
entrez:
13
9
2021
Statut:
ppublish
Résumé
Breast cancer is one of the most common cancers worldwide among women, and angiogenesis has an important effect on its growth and metastasis. Glipizide, which is a widely used drug for type 2 diabetes mellitus, has been reported to inhibit tumor growth and metastasis by upregulating the expression of natriuretic peptide receptor A (NPRA). Atrial natriuretic peptide (ANP), the receptor of NPRA, plays an important role in angiogenesis. The purpose of this study was to explore the effect of glipizide combined with ANP on breast cancer growth and metastasis. This study aimed at investigating the effect of glipizide combined with ANP on breast cancer. Glipizide, ANP, or glipizide combined with ANP was intraperitoneally injected into MMTV-PyMT mice. To explore whether the anticancer efficacy of glipizide combined with ANP was correlated with angiogenesis, a tube formation assay was performed. Glipizide combined with ANP was found to inhibit breast cancer growth and metastasis in MMTV-PyMT mice, which spontaneously develop breast cancer. Furthermore, the inhibitory effect of ANP combined with glipizide was better than that of glipizide alone. ANP combined with glipizide significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) by suppressing vascular endothelial growth factor (VEGF)/VEGFR2 (vascular endothelial growth factor receptor 2) signaling. These results demonstrate that glipizide combined with ANP has a greater potential than glipizide alone to be repurposed as an effective agent for the treatment of breast cancer by targeting tumor-induced angiogenesis.
Sections du résumé
BACKGROUND
Breast cancer is one of the most common cancers worldwide among women, and angiogenesis has an important effect on its growth and metastasis. Glipizide, which is a widely used drug for type 2 diabetes mellitus, has been reported to inhibit tumor growth and metastasis by upregulating the expression of natriuretic peptide receptor A (NPRA). Atrial natriuretic peptide (ANP), the receptor of NPRA, plays an important role in angiogenesis. The purpose of this study was to explore the effect of glipizide combined with ANP on breast cancer growth and metastasis.
METHODS
This study aimed at investigating the effect of glipizide combined with ANP on breast cancer. Glipizide, ANP, or glipizide combined with ANP was intraperitoneally injected into MMTV-PyMT mice. To explore whether the anticancer efficacy of glipizide combined with ANP was correlated with angiogenesis, a tube formation assay was performed.
RESULTS
Glipizide combined with ANP was found to inhibit breast cancer growth and metastasis in MMTV-PyMT mice, which spontaneously develop breast cancer. Furthermore, the inhibitory effect of ANP combined with glipizide was better than that of glipizide alone. ANP combined with glipizide significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) by suppressing vascular endothelial growth factor (VEGF)/VEGFR2 (vascular endothelial growth factor receptor 2) signaling.
CONCLUSION
These results demonstrate that glipizide combined with ANP has a greater potential than glipizide alone to be repurposed as an effective agent for the treatment of breast cancer by targeting tumor-induced angiogenesis.
Identifiants
pubmed: 34515012
pii: ACAMC-EPUB-117822
doi: 10.2174/1871520621666210910085733
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Vascular Endothelial Growth Factor A
0
Atrial Natriuretic Factor
85637-73-6
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Glipizide
X7WDT95N5C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1735-1741Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.