Schisandrin B suppresses osteosarcoma lung metastasis in vivo by inhibiting the activation of the Wnt/β‑catenin and PI3K/Akt signaling pathways

Oncol Rep. 2022 Mar;47(3):50. doi: 10.3892/or.2022.8261. Epub 2022 Jan 14.

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor worldwide and is associated with a poor prognosis, often being accompanied by lung metastasis at an early stage. At present, there are several side‑effects associated with the OS clinical treatment of OS, with the treatment effects often being unsatisfactory. Thus, there is an urgent need for the development of safe and effective novel drugs for the treatment of OS. Schisandrin B (Sch B) has been previously demonstrated to exhibit antitumor properties. The present study was focused on the effects of Sch B on OS cells (143B, MG63, Saos2 and U2OS) in vitro and in vivo, and also on its possible antitumor mechanisms. In cell experiments, it was revealed that Sch B inhibited OS cell proliferation, migration and invasion, and increased OS cell apoptosis. As regards its biosafety, no notable effects of Sch B on the vitality of normal cells were observed. Mechanistically, it was demonstrated that Sch B blocked OS cell proliferation in the G1 phase. Subsequently, by using established animal models, it was revealed that Sch B significantly inhibited OS growth and lung metastasis in vivo. In summary, the results of the present study revealed that Sch B inhibited OS cell proliferation, migration and invasion, and promoted apoptosis via the inhibition of the Wnt/β‑catenin and PI3K/Akt signaling pathways, without causing any noticeable toxic effects on healthy cells at the therapeutic concentrations used. These findings suggest that Sch B has potential for use as a novel agent for the clinical treatment of OS.

Keywords: PI3K; Schisandrin B; Wnt/β‑catenin; lung metastasis; osteosarcoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cyclooctanes / pharmacology
  • Disease Models, Animal
  • Humans
  • Lignans / pharmacology*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Mice
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Polycyclic Compounds / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Wnt Signaling Pathway / drug effects*
  • beta Catenin / metabolism*

Substances

  • Antineoplastic Agents
  • Cyclooctanes
  • Lignans
  • Polycyclic Compounds
  • beta Catenin
  • schizandrin B
  • Proto-Oncogene Proteins c-akt

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant no. 81873998).