SBF-1 preferentially inhibits growth of highly malignant human liposarcoma cells

J Pharmacol Sci. 2018 Dec;138(4):271-278. doi: 10.1016/j.jphs.2018.10.009. Epub 2018 Oct 24.

Abstract

Frequent local recurrence and metastasis are generally involved in human liposarcoma, but the management is a challenge. There is an urgent need for improved effective therapy. In the present study, we reported that SBF-1, a steroidal glycoside, inhibited the growth of cultured highly malignant human liposarcoma SW872-S cells in vitro and in vivo. SBF-1 down-regulated the phosphorylation of protein kinase B (AKT) and thus reduced cell adhesion to fibronectin and laminin. Then we found that SBF-1 inhibited the expression of oxysterol binding protein (OSBP) in SW872-S cells, indicating that OSBP may be involved in malignant liposarcoma cell survival. Cancer cell growth and AKT phosphorylation were inhibited significantly upon knockdown of OSBP in SW872-S cells in vitro. Taken together, these results suggest that SBF-1 causes an apparent loss of OSBP function in SW872-S cells, resulting in growth inhibition. Based on our findings, OSBP serves as a potential therapeutic target for human liposarcoma.

Keywords: Malignant liposarcoma; SBF-1; SW872-S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cholestenones / pharmacology*
  • Cholestenones / therapeutic use
  • Female
  • Humans
  • Liposarcoma / drug therapy
  • Liposarcoma / genetics
  • Liposarcoma / metabolism*
  • Liposarcoma / pathology
  • Mice, Nude
  • Oxysterol Binding Proteins
  • Receptors, Steroid / antagonists & inhibitors*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism
  • Saponins / pharmacology*
  • Saponins / therapeutic use

Substances

  • Antineoplastic Agents
  • Cholestenones
  • Receptors, Steroid
  • SBF-1 compound
  • Saponins
  • Oxysterol Binding Proteins