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

Feng,Tao; Qiao,Guanglei; Feng,Li; Qi,Weixiang; Huang,Yujing; Yao,Yang; Shen,Zan

doi:10.3892/mmr.2014.2618

December-2014 Volume 10 Issue 6

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December-2014 Volume 10 Issue 6

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Article

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

Authors:
- Tao Feng
- Guanglei Qiao
- Li Feng
- Weixiang Qi
- Yujing Huang
- Yang Yao
- Zan Shen
View Affiliations / Copyright

Affiliations: Department of Oncology, Affiliated People's 6th Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China, Department of Pharmacy, The Donggang People's Hospital, Rizhao, Shandong 276800, P.R. China
Pages: 2985-2992
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Published online on: October 9, 2014

https://doi.org/10.3892/mmr.2014.2618
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Abstract

Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. Numerous patients are unable to be cured due to the development of resistance of the osteosarcoma cells to chemotherapeutic drugs. Therefore, reversion of drug resistance is urgently required for the treatment of osteosarcoma. Arsenic trioxide (As2O3) is an active ingredient in Traditional Chinese Medicine, but the therapeutic potential of As2O3 in osteosarcoma remains largely unexplored. The current study investigated the effects of As2O3 on MG63 osteosarcoma cells using a cell proliferation assay, flow cytometric analysis of the cell cycle and cell apoptosis, reverse transcription polymerase chain reaction to detect stathmin mRNA expression levels and western blot analysis to detect the stathmin protein expression levels. As2O3 and doxorubicin (ADM) combination treatment markedly inhibited cell proliferation in ADM-resistant MG63 (MG63/dox) osteosarcoma cells, clearly induced G2/M phase cell cycle arrest and increased the number of apoptotic MG63/dox cells. Furthermore, stathmin expression was found to be downregulated in MG63/dox cells and was sensitive to ADM treatment. Additional investigation revealed that the downregulation of stathmin expression in MG63/dox cells by stathmin small interfering RNA significantly enhanced the reversion of ADM resistance in MG63/dox by As2O3. The data indicated that As2O3 reversed ADM resistance in MG63/dox cells through downregulation of stathmin and may be a potential drug for the treatment of ADM-resistant osteosarcoma.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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Abstract

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