Differentially activated Src kinase in chemo-naïve human primary osteosarcoma cells and effects of a Src kinase inhibitor

Biofactors. 2017 Nov;43(6):801-811. doi: 10.1002/biof.1382. Epub 2017 Aug 8.


The therapeutic treatment of osteosarcoma (OS), a rare malignant teenage cancer of the skeletal system, still represents a great challenge as patient survival after conventional protocol chemotherapy treatment has not improved in the last four decades leaving poor patient prognoses. Therefore, many efforts have been done to find increasingly reliable OS cell models and to identify "druggable" targets in OS, in order to identify novel effective therapeutic approaches and treatment strategies. In this contest, the more successful use of patient-derived cell cultures in respect to human commercial lines and findings of Src kinase deregulation in cancer, prompted us to study for the first time the activation state of Src and the potential activity of our Src inhibitor SI-83 in a number of chemo-naïve patient-derived primary OS cells. We here demonstrate that Src is hyperactivated in OS cells in respect to the nonmalignant counterpart and that SI-83 is able to strongly decrease cell viability, proliferation, Src416 phosphorylation, and cell migration. © 2017 BioFactors, 43(6):801-811, 2017.

Keywords: Src activation; Src inhibitors; Src phosphorylation; migration; osteosarcoma chemo-naïve; proliferation; pyrazolo[3,4-d]pyrimidine derivative; viability.

MeSH terms

  • Apoptosis / drug effects
  • Bone Neoplasms / enzymology
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Enzyme Activation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Osteoblasts / drug effects*
  • Osteoblasts / enzymology
  • Osteoblasts / pathology
  • Osteosarcoma / enzymology
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • Phosphorylation / drug effects
  • Primary Cell Culture
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • Signal Transduction
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism


  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • SI-83 compound
  • src-Family Kinases