A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Tumor progression relies heavily on angiogenesis, a process driven by vascular endothelial growth factor (VEGF).
• Targeting the VEGF-VEGF receptor system is a key strategy in anti-cancer therapy.
• Previous research identified a hexapeptide (RK6) and its D-form derivative (dRK6) that inhibit VEGF binding and tumor growth.

Purpose of the Study:

• To develop a more potent and serum-stable anti-angiogenic peptide.
• To evaluate the enhanced anti-VEGF and anti-tumor activity of a novel branched dimeric peptide, MAP2-dRK6.

Main Methods:

• Synthesis and characterization of the branched dimeric peptide MAP2-dRK6.
• In vitro assays assessing inhibition of VEGF receptor binding, endothelial cell proliferation, ERK signaling, migration, and tube formation.
• In vivo studies evaluating the anti-tumor efficacy of MAP2-dRK6 in a colorectal cancer model.

Main Results:

• MAP2-dRK6 demonstrated superior inhibition of VEGF binding compared to dRK6.
• MAP2-dRK6 effectively suppressed endothelial cell proliferation, signaling, migration, and tube formation induced by VEGF.
• In vivo, MAP2-dRK6 significantly inhibited tumor growth by suppressing angiogenesis and inducing tumor cell apoptosis.

Conclusions:

• MAP2-dRK6 exhibits enhanced anti-VEGF and anti-tumor activity.
• MAP2-dRK6 represents a promising therapeutic candidate for VEGF-related angiogenic diseases.
• Further development of MAP2-dRK6 could lead to novel anti-cancer drugs.