Evidence map›Paper›PMID 40790610›Full record

ArticleBMC pharmacology & toxicology2025

The inhibitory effect of tyrosine kinase inhibitors on angiogenesis in zebrafish and interrelationship with the activation of the PI3K/AKT pathway.

Lili Yang, Xiaotian Liu

Abstract read
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Article in BMC pharmacology & toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Lili YangNingbo Key Laboratory of Medical Research on Blinding Eye Diseases, Ningbo Eye Institute, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, 315040, China.
Xiaotian LiuNingbo Key Laboratory of Medical Research on Blinding Eye Diseases, Ningbo Eye Institute, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, 315040, China. 523755781@qq.com.

Funding

the Medical Health Science and Technology Project of Zhejiang Province 2024KY364
6 · The paper itself

Abstract

backgroundTo evaluate the effects of tyrosine kinase inhibitors (TKIs) Dovitinib, Lapatinib, and Telatinib on angiogenesis in zebrafish, and to explore the regulatory mechanism of PI3K/AKT pathway activator SC79 on these inhibitory effects.

methodsTransgenic Fli-1:EGFP zebrafish embryos were used to observe the development and morphological changes of intersegmental vessels (ISVs) by fluorescence microscopy. Real-time fluorescence quantitative PCR was employed to detect the expression of angiogenesis-related genes including kdrl, flt1, vegfaa, akt2, and pik3r1. After determining the maximum tolerated concentration (MTC) of each compound, the effects of single-drug treatment and SC79 co-treatment on vascular development and gene expression were observed.

resultsDovitinib (0.488 µM) and Telatinib (0.031 µM) significantly reduced the number (by 16.9% and 33.8%, respectively, P < 0.001) and length (by 14.9% and 23.3%, respectively, P < 0.001) of complete ISVs, while Lapatinib (1.95 µM) showed no significant inhibitory effect. Gene expression analysis revealed that Dovitinib mainly downregulated flt1 expression (P < 0.01), whereas Telatinib more broadly downregulated kdrl (P < 0.05), flt1 (P < 0.001), and akt2 (P < 0.01) expression. SC79 (2.44 nM) promoted angiogenesis, increasing ISV number (P < 0.01) and length (P < 0.05), while upregulating kdrl (2.03-fold, P < 0.001), flt1 (1.31-fold, P < 0.05), vegfaa (1.45-fold, P < 0.01), akt2 (1.64-fold, P < 0.01), and pik3r1 (1.48-fold, P < 0.05) expression. Co-treatment experiments showed that all three TKIs could counteract SC79’s pro-angiogenic effects to varying degrees, with Telatinib showing the strongest effect. Under SC79 co-treatment conditions, all TKIs significantly downregulated kdrl expression (P < 0.001), but had differential effects on other genes: Dovitinib mainly downregulated flt1 (P < 0.05), Lapatinib specifically downregulated vegfaa (P < 0.01), akt2 (P < 0.05), and pik3r1 (P < 0.05), while Telatinib simultaneously downregulated flt1 (P < 0.01), akt2 (P < 0.05), and pik3r1 (P < 0.01).

conclusionsDovitinib and Telatinib exhibit significant anti-angiogenic effects, while Lapatinib is less effective. Different TKIs inhibit angiogenesis by regulating different signaling molecules: Dovitinib primarily targets VEGF receptors, Telatinib targets both receptors and the downstream PI3K/AKT pathway, and Lapatinib shows inhibitory effects on VEGF ligand expression in the SC79 background. SC79 promotes angiogenesis by activating the PI3K/AKT pathway and partially reverses the inhibitory effects of TKIs. These findings provide new insights for targeted therapy of abnormal angiogenesis in ophthalmic diseases, suggesting that precise regulation of angiogenesis may be achieved by modulating the balance between TKIs and the PI3K/AKT signaling pathway.

Indexed as

AngiogenesisNeovascularization, PhysiologicPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktAnimalsAnimals, Genetically ModifiedBenzimidazolesLapatinibQuinolonesSignal TransductionTyrosine Kinase InhibitorsZebrafish4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-oneBenzimidazolesLapatinibPhosphatidylinositol 3-KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktQuinolonesTyrosine Kinase InhibitorsAngiogenesisIntersegmental vesselsPI3K/AKT pathwayTyrosine kinase inhibitorsZebrafish

Identifiers

PMID40790610
PMCPMC12341200

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.