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HMGB1-mediated autophagy decreases sensitivity to oxymatrine in SW982 human synovial sarcoma cells

Yongsong Cai1, Peng Xu2, Le Yang2

  • 1Department of Orthopaedics of the First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.

Scientific Reports
|November 30, 2016
PubMed

Insights

Oxymatrine (OMT) shows antitumor effects in human synovial sarcoma cells by increasing autophagy. This autophagy, mediated by high mobility group box protein 1 (HMGB1), protects cells; inhibiting it enhances OMT

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Oxymatrine (OMT), an alkaloid from Sophora flavescens, has known antitumor properties.
  • The effects of OMT on human synovial sarcoma and its underlying mechanisms remain uninvestigated.

Purpose of the Study:

  • To investigate the antitumor activity of OMT on SW982 human synovial sarcoma cells.
  • To determine the role of high mobility group box protein 1 (HMGB1)-mediated autophagy in OMT's therapeutic effects.

Main Methods:

  • Cell culture of SW982 human synovial sarcoma cells.
  • Treatment with Oxymatrine (OMT), autophagy inhibitors (3-MA, ATG7 siRNA), and HMGB1 inhibitors (HMGB1-siRNA).
  • Analysis of cell apoptosis, autophagy markers, and protein expression (HMGB1, p-Akt, p-mTOR).

Main Results:

  • OMT demonstrated antitumor activity and induced autophagy in SW982 cells.
  • Inhibition of autophagy increased OMT-induced apoptosis, indicating a protective role for autophagy.
  • OMT increased HMGB1 expression; HMGB1 inhibition reduced OMT-induced autophagy and increased apoptosis, suggesting HMGB1's role in autophagy regulation via the Akt/mTOR pathway.

Conclusions:

  • OMT exhibits antitumor effects on human synovial sarcoma cells, partly through HMGB1-mediated autophagy.
  • OMT-induced autophagy is a protective mechanism; its inhibition enhances OMT's cytotoxicity.
  • Combining OMT with autophagy or HMGB1 inhibitors may improve treatment efficacy for human synovial sarcoma.

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