Antimetastatic effects of calycosin on osteosarcoma and the underlying mechanism

Biofactors. 2019 Nov;45(6):975-982. doi: 10.1002/biof.1545. Epub 2019 Jul 19.

Abstract

Osteosarcoma (OS) refers to a malignant tumor with potential invasiveness and metastasis; however, the current chemotherapy of OS is lacking. Thus, the alternative drug for treating OS is urgent to explore. Calycosin (CC) is evidenced in our previous study to play the anti-OS benefits for suppressing cancer cell proliferation. Consequently, further investigation of CC-medicated anti-invasive and metastatic effects against OS is needed. In the current study, the clinical samples of OS patients were collected for biological and staining assays, such as enzyme-linked immunosorbent assay and polymerase chain reaction. Meanwhile, the cell line and tumor-bearing nude mice were employed in assessing antimetastatic effects of CC against OS through biochemical tests and immunoassays. As a result, the OS patients exhibited upregulated neoplastic expressions of matrix metalloproteinase 2 (MMP2) and proliferating cell nuclear antigen (PCNA), cellular mRNAs and proteins of inhibitor of nuclear factor kappa-B alpha (IκBα), and epithelial cell transforming sequence 2 (ECT2). In cell-line study, CC-treated human OS cells exhibited induced cell apoptosis, reduced cell proliferation, and cellular MMP2 and PCNA concentration, inhibited cell migration, lowered expressions of IκBα ECT2 mRNAs, and proteins. In tumor-bearing nude mice study, CC-treated mice resulted in the dose-dependent reductions of tumor weights and intracellular MMP2 contents. As shown in further assays, neoplastic expressions of interleukin 6 protein, IκBα, ECT2 mRNAs, and proteins were downregulated dose-dependently in CC-treated tumor-bearing mice. In conclusion, these investigative findings suggest that CC may play the potential anti-invasive benefits against OS through suppressing metastasis-associated IκBα/ECT2 molecular pathway.

Keywords: ECT2; IκBα; calycosin; metastasis; osteosarcoma.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Isoflavones / pharmacology*
  • Matrix Metalloproteinase 2 / genetics
  • Mice
  • NF-KappaB Inhibitor alpha / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • Proto-Oncogene Proteins / genetics*
  • Transplantation, Heterologous

Substances

  • ECT2 protein, human
  • Isoflavones
  • Proto-Oncogene Proteins
  • 7,3'-dihydroxy-4'-methoxyisoflavone
  • NF-KappaB Inhibitor alpha
  • MMP2 protein, human
  • Matrix Metalloproteinase 2