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Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells

Tao Feng1, Guanglei Qiao1, Li Feng2

  • 1Department of Oncology, Affiliated People's 6th Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China.

Molecular Medicine Reports
|October 14, 2014
PubMed

Insights

Arsenic trioxide (As2O3) can reverse chemotherapy drug resistance in osteosarcoma cells. This study shows As2O3 downregulates stathmin, a protein linked to drug resistance, offering a new treatment strategy for resistant osteosarcoma.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Osteosarcoma is a common pediatric bone cancer.
  • Drug resistance limits treatment efficacy in osteosarcoma.
  • Arsenic trioxide (As2O3), a component of Traditional Chinese Medicine, has unexplored therapeutic potential.

Purpose of the Study:

  • To investigate the effects of As2O3 on drug-resistant osteosarcoma cells.
  • To explore the role of stathmin in As2O3-mediated drug resistance reversal.

Main Methods:

  • Cell proliferation assays, flow cytometry (cell cycle, apoptosis), RT-PCR, and Western blot analysis were used.
  • MG63 osteosarcoma cells, including doxorubicin-resistant (MG63/dox) cells, were treated with As2O3 and doxorubicin (ADM).
  • Stathmin expression was modulated using small interfering RNA (siRNA).

Main Results:

  • Combination treatment with As2O3 and ADM inhibited proliferation and induced G2/M phase arrest and apoptosis in MG63/dox cells.
  • Stathmin expression was downregulated in MG63/dox cells and sensitive to ADM.
  • Downregulation of stathmin by siRNA enhanced As2O3's ability to reverse ADM resistance.

Conclusions:

  • As2O3 reverses doxorubicin resistance in osteosarcoma cells by downregulating stathmin.
  • As2O3 shows potential as a therapeutic agent for treating drug-resistant osteosarcoma.

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