ArticlePharmaceuticals (Basel, Switzerland)2023
A VEGFB-Based Peptidomimetic Inhibits VEGFR2-Mediated PI3K/Akt/mTOR and PLCγ/ERK Signaling and Elicits Apoptotic, Antiangiogenic, and Antitumor Activities.
Article in Pharmaceuticals (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Advances in the molecular signaling mechanisms of VEGF/VEGFR2 in fundus neovascularization disease (Review).Experimental and therapeutic medicine · 2025Review
- M2 macrophage-derived exosomes promote cell proliferation, migration and EMT of non-small cell lung cancer by secreting miR-155-5p.Molecular and cellular biochemistry · 2025Article
- tRF-34-P4R8YP9LON4VHM Promotes Hepatocellular Carcinoma Progression and Tumour Cell-Induced Angiogenesis via the MEK/ERK Pathway.Journal of cellular and molecular medicine · 2025Article
- Vitamin C Mediates IGFBP7 to Alleviate Chronic Atrophic Gastritis via the HIF-1α/VEGF Pathway.Journal of cellular and molecular medicine · 2025Article
- The molecular mechanism of gemcitabine in inhibiting the HIF-1α/VEGFB/FGF2/FGFR1 signaling pathway for ovarian cancer treatment.Discover oncology · 2025Article
- Synergistic Efficacy of Dual-Target HSA-Based Delivery for HER and VEGFR Co-Blockade in Triple-Negative Breast Cancer.International journal of molecular and cellular medicine · 2025Article
- The role of macrophages in hypertrophic scarring: molecular to therapeutic insights.Frontiers in immunology · 2025Review
- Long noncoding RNA VPS9D1-AS1 promotes angiogenesis in colorectal cancer by regulating the VEGFA signalling pathway.American journal of cancer research · 2025Article
- Review
- Microcystin-LR activates serine/threonine kinases and alters the phosphoproteome in human HepaRG cells.Toxicon : official journal of the International Society on Toxinology · 2024Article
- A multifunctional injectable, self-healing, and adhesive hydrogel-based wound dressing stimulated diabetic wound healing with combined reactive oxygen species scavenging, hyperglycemia reducing, and bacteria-killing abilities.Journal of nanobiotechnology · 2024Article
- Synthesis, Radiolabeling, and Biodistribution Study of a Novel DOTA-Peptide for Targeting Vascular Endothelial Growth Factor Receptors in the Molecular Imaging of Breast Cancer.Pharmaceutics · 2024Article
- Article
- Roles of endothelial cell specific molecule‑1 in tumor angiogenesis (Review).Oncology letters · 2024Review
- Apoptosis enhancement in MCF-7 cells: Synergistic effects of doxorubicin and the novel sulfonamide Zm-093.International journal of immunopathology and pharmacologyArticle
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor receptor 2 (VEGFR2) mediates VEGFA signaling mainly through the PI3K/AKT/mTOR and PLCγ/ERK1/2 pathways. Here we unveil a peptidomimetic (VGB3) based on the interaction between VEGFB and VEGFR1 that unexpectedly binds and neutralizes VEGFR2. Investigation of the cyclic and linear structures of VGB3 (named C-VGB3 and L-VGB3, respectively) using receptor binding and cell proliferation assays, molecular docking, and evaluation of antiangiogenic and antitumor activities in the 4T1 mouse mammary carcinoma tumor (MCT) model showed that loop formation is essential for peptide functionality. C-VGB3 inhibited proliferation and tubulogenesis of human umbilical vein endothelial cells (HUVECs), accounting for the abrogation of VEGFR2, p-VEGFR2 and, subsequently, PI3K/AKT/mTOR and PLCγ/ERK1/2 pathways. In 4T1 MCT cells, C-VGB3 inhibited cell proliferation, VEGFR2 expression and phosphorylation, the PI3K/AKT/mTOR pathway, FAK/Paxillin, and the epithelial-to-mesenchymal transition cascade. The apoptotic effects of C-VGB3 on HUVE and 4T1 MCT cells were inferred from annexin-PI and TUNEL staining and activation of P53, caspase-3, caspase-7, and PARP1, which mechanistically occurred through the intrinsic pathway mediated by Bcl2 family members, cytochrome c, Apaf-1 and caspase-9, and extrinsic pathway via death receptors and caspase-8. These data indicate that binding regions shared by VEGF family members may be important in developing novel pan-VEGFR inhibitors that are highly relevant in the pathogenesis of angiogenesis-related diseases.
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