Relaxin promotes in vitro tumour growth, invasion and angiogenesis of human Saos-2 osteosarcoma cells by AKT/VEGF pathway

Eur Rev Med Pharmacol Sci. 2013 May;17(10):1345-50.

Abstract

Objectives: In the present study, we determine the role of relaxin on cellular growth, invasion and angiogenesis of osteosarcoma Saos-2 cells in vitro, and discuss the molecular mechanisms of this action.

Materials and methods: Saos-2 cells were transfected with Akt1/2 siRNA or VEGF siRNA for 24 hours then treated with 10-100 ng/mL recombinant human relaxin-2 (rh-RLN) for 48 h. MTT, matrigel and bone marrow-derived endothelial cells (BMDECs) was used for cell proliferation, invasion and angiogenesis assay. Western blot was used for relaxin-2, pAKT and VEGF protein assay.

Results: The results showed treatment with 10-100 ng/mL rh-RLN resulted in 18%, 48%, 107%, 212% increase in cell proliferation, respectively (vs control, *p < 0.05;**p < 0.01), the relative invasive cells was 1.4;1.9;2.6;4.8 (control was defined to 1) (vs control, #p < 0.01; ##p < 0.001) and the relative anglogenic branch points in Saos-2 cells was 1.04;1.36;1.69;2.10 (control was defined to 1.00) (vs control, *p < 0.05; **p < 0.01). Furthermore, treatment with rh-RLN exhibited a significant increase in the expression level of pAKT and VEGF proterin in dose-dependent manner. Saos-2 cells were transfected with AKT1/2 siRNA for 24 h. No significant increase of VEGF protein expression was shown after rh-RLN treatment.

Conclusions: These results suggested that rh-RLN could promoted proliferation, invasion and angiogenesis by upregulation pAKT-dependent VEGF expression.

MeSH terms

  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / etiology*
  • Osteosarcoma / pathology*
  • Proto-Oncogene Proteins c-akt / physiology*
  • Recombinant Proteins / pharmacology
  • Relaxin / pharmacology*
  • Signal Transduction / physiology
  • Vascular Endothelial Growth Factor A / physiology*

Substances

  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Relaxin
  • Proto-Oncogene Proteins c-akt