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. 2015 May 1;8(5):5387-94.
eCollection 2015.

Inhibitory effect of midkine-binding peptide on tumor proliferation and migration

Hui-Lian Huang  1 , Jian-Fen Shen  2 , Li-Shan Min  1 , Jin-Liang Ping  3 , Yong-Liang Lu  4 , Li-Cheng Dai  1
Affiliations

Inhibitory effect of midkine-binding peptide on tumor proliferation and migration

Hui-Lian Huang et al. Int J Clin Exp Pathol. .

Abstract

Background: To investigate the inhibitory effect of midkine-binding peptides on human umbilical vein endothelial cells (HUVECs) proliferation and angiogenesis of xenograft tumor.

Methods: The midkine-binding peptides were panned by Ph.D.-7(™) Phage Display Peptide Library Kit, and the specific binding activities of positive clones to target protein were examined by phage ELISA. The effect of midkine-binding peptides on proliferation of HUVECs was confirmed by MTT test. The xenograft tumor model was formed in BALB/c mice with the murine hepatocarcinoma cells H22 (H22). Microvessel density (MVD) was analyzed by immunohistochemistry of factor VIII staining.

Results: Midkine-binding peptides have the inhibitory effects on tumor angiogenesis, a proliferation assay using human umbilical vein endothelial cells (HUVECs) indicated that particular midkine-binding peptides significantly inhibited the proliferation of the HUVECs. Midkine-binding peptides were also observed to efficiently suppress angiogenesis induced by murine hepatocarcinoma H22 cells in BALB/c nude mice.

Conclusion: The midkine-binding peptides can inhibit solid tumor growth by retarding the formation of new blood vessels. The results indicate that midkine-binding peptides may represent potent anti-angiogenesis agents in vivo.

Keywords: Midkine; angiogenesis; peptide.

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Figures

Figure 1
Figure 1
Specific binding of selected phage clones to the anti-M13 antibody. 29 clones bound to the target protein; there were 14 cyclic peptides (No. 1-14) (A) and 15 linear peptides (No. 15-29) (B). The original phage peptide library without selection, represented as No. 0, the original library without selection was used as negative control. All of the treatments were performed in triplicate.
Figure 2
Figure 2
Effects of midkine-binding peptides on the proliferation of HUVECs. Midkine-binding peptides significantly inhibited the proliferation of HUVECs. Among the six peptides examined, MK-P3 showed the highest inhibitory activity, the non-specific peptide was examined as the negative control. All of the treatments were repeated six times.
Figure 3
Figure 3
Effects of midkine-binding peptides treatment on tumor angiogenesis. The representative images of immunohistochemistry stained for microvessels (factor VIII) in a xenograft tumor (×200). A. Sections of tumors from PBS treatment. B. Sections of tumors from non-specific peptide treatment as negative control. C. Sections of tumors following treatment with MK-P3. D. Sections of tumors from treatment with MK-P.
See this image and copyright information in PMC

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