VEGI174 protein and its functional domain peptides exert antitumour effects on renal cell carcinoma

Int J Oncol. 2019 Jan;54(1):390-398. doi: 10.3892/ijo.2018.4632. Epub 2018 Nov 12.

Abstract

Vascular endothelial growth inhibitor (VEGI) has been identified as an anti‑angiogenic cytokine. However, the effects of VEGI174 protein, and its functional domain peptides V7 and V8, on renal cell carcinoma (RCC) remain unknown. In the present study, the protein and peptides were biosynthesised as experimental agents. The A498 and 786‑O RCC cell lines, and an established mouse xenograft model, were separately treated with VEGI174, V7 or V8. Cellular functions, including proliferation, migration and invasion, were subsequently detected. Cell migration and invasion were monitored using the xCELLigence system. Furthermore, tumour growth and mouse behaviours, including mobility, appetite and body weight, were assessed. The results demonstrated that VEGI174, V7 and V8 inhibited the proliferation, migration and invasion of A498 and 786‑O cell lines when administered at concentrations of 1 and 100 pM, 10 nM and 1 µM. The inhibitory effects exhibited dose‑ and time‑dependent antitumour activity. Furthermore, VEGI174, V7 and V8 inhibited tumour growth in A498 and 786‑O xenograft mice. In the A498 xenografts, the tumour growth inhibition (TGI) rates in the VEGI174‑, V7‑ and V8‑treated groups were 71, 20 and 31%, respectively. In the 786‑O xenografts, the TGI rates in the VEGI174‑, V7‑ and V8‑treated groups were 34, 26 and 31%, respectively. There was no significant loss in body weight and no cases of mortality were observed for all treated mice. In conclusion, VEGI174, V7 and V8 exhibited potential antitumour effects and were well tolerated in vivo. V7 and V8, as functional domain peptides of the VEGI174 protein, may be studied for the future treatment of RCC.

Keywords: renal cell carcinoma; vascular endothelial growth inhibitor; peptide; in vitro; in vivo.

MeSH terms

  • Alternative Splicing*
  • Animals
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Mice
  • Peptides / administration & dosage*
  • Peptides / pharmacology
  • Protein Domains
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / chemistry*
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Peptides
  • TNFSF15 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 15