Oridonin inhibits the proliferation, migration and invasion of human osteosarcoma cells via suppression of matrix metalloproteinase expression and STAT3 signalling pathway

J BUON. 2019 May-Jun;24(3):1175-1180.

Abstract

Purpose: Oridonin, a diterpenoid, has been reported to exhibit anticancer activity against a wide range of cancer types.In this study, the effect Oridonin was examined against human osteosarcoma cells.

Methods: The human osteosarcoma cells U2OS were treated with various concentrations of Oridonin from 0-200 μM for 24 h. The anti-proliferative effects of Oridonin were measured by cell viability assay. DAPI and annexin V/propidium iodide (PI) assays were employed to examine the induction of apoptosis. Transwell assay was performed to examine the cell migration and invasion. Expression analysis was performed by western blot.

Results: Oridonin inhibited the proliferation of U2OScells and exhibited an IC50 of 30 µM. The antiproliferative effects were mainly found to be due to induction of apoptosis as indicated by DAPI staining. Moreover, the annexin V/PI staining showed that the percentage of the apoptotic cells increased with increase in the concentration of Oridonin. The induction of apoptosis was also related with upregulation of Bax, Caspase 3 and 9 expression and downregulation of Bcl-2. Oridonin was also found to cause significant decrease in the expression of MMP-2, 3 and 9 concentration-dependently. Transwell assay showed that Oridonin inhibited the migration and invasion of the U2OS cells.

Conclusion: It is concluded that Oridonin exhibits significant antiproliferative effects on the osteosarcoma cells and may prove essential in the development of systemic therapy for osteosarcoma.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Diterpenes, Kaurane / pharmacology
  • Diterpenes, Kaurane / therapeutic use*
  • Humans
  • Matrix Metalloproteinases / metabolism*
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction

Substances

  • Diterpenes, Kaurane
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • oridonin
  • Matrix Metalloproteinases