Journal of Practical Oncology ›› 2025, Vol. 39 ›› Issue (2): 116-125.doi: 10.11904/j.issn.1002-3070.2025.02.007

• Basic Research • Previous Articles     Next Articles

The effect of anti-angiogenic nanopeptides on delaying the progression in clear cell renal carcinoma by inhibiting the dual signaling pathways of VEGF and TIE-2

LIU Pan1,2, KONG Bin2,3, ZANG Jiahui2,3, WANG Xinyue2,3, SUN Yue1,2, WANG Lu2,3, XU Wanhai2,4   

  1. 1. Department of Urology,Harbin Medical University Cancer Hospital,Harbin 150081, China;
    2. NHC Key Laboratory of Molecular Probe and Targeted Theranostics;
    3. Department of Urology,The Fourth Hospital of Harbin Medical University;
    4. Department of Urology,the Second Affiliated Hospital of Harbin Medical University
  • Received:2024-12-12 Revised:2025-03-10 Online:2025-04-28 Published:2025-05-06

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Abstract: Objective A targeted nanopeptides(VEGF/TIE-2 targeted nanopeptides,VTN)that simultaneously inhibits vascular endothelial growth factor(VEGF)/ tyrosine kinase with immunoglobulin-like and EGF-like domains-2(TIE-2)signaling pathways were designed and synthesized,and explore its inhibitory effect on angiogenesis in renal clear cell carcinoma(ccRCC). Methods VTN and non-self-assembling control VTN-C were prepared by solid-phase peptide synthesis technology,and the molecular structures of VTN and VTN-C were analyzed by electrospray ionization mass spectrometry(ESI-MS).The CCK-8 method was used to evaluate the effect of VTN on the cell viability of human umbilical vein endothelial cells(HUVEC).The cell scratch assay,Transwell invasion assay and angiogenesis assay were used to detect the inhibitory effects of VTN on migration,invasion and angiogenesis of HUVEC.Western blot was used to detect the effect of VTN on the phosphorylation of downstream proteins of VEGF and TIE-2 signaling pathways.A 786-O cell mouse model was established,and the effects of VTN on tumor angiogenesis and tumor progression were observed through animal experiments. Results ESI-MS showed that the main charge state peaks of both synthesized VTN and VVTN-C pointed to the same molecular weight,which was highly consistent with the corresponding theoretical molecular mass.Immunofluorescence showed that VTN co-localized with VEGF and TIE-2.VTN combined with MMP-2 could significantly inhibit the activity of HUVEC(P＜0.001).The cell invasion rate and scratch closure rate in the VTN group were reduced by(78.30±1.35)% and(37.09±3.49)% compared those in the PBS group,respectively(P＜0.001).Angiogenesis experiments showed that VTN could significantly inhibit the angiogenesis of HUVEC(P＜0.001).Western blot showed that VTN significantly inhibited the phosphorylation of Akt and ERK(P＜0.001).The results from animal experiments showed that tumor volume in the VTN group was decreased by(87.16±1.30)% compared with the control group,and the CD31-positive area was reduced(P＜0.001). Conclusion VTN significantly blocks ccRCC angiogenesis and delays tumor progression by inhibiting VEGF and TIE-2 signaling pathways and downregulating Akt and ERK phosphorylation.

Key words: Renal clear cell carcinoma, Nanopeptide, Angiogenesis, Vascular endothelial growth factor, Tyrosine protein kinase with immunoglobulin-like and epidermal growth factor-like domains-2

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