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Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells.
Mol Med Rep. 2014 Dec; 10(6):2985-92.MM

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25310700

Citation

Feng, Tao, et al. "Stathmin Is Key in Reversion of Doxorubicin Resistance By Arsenic Trioxide in Osteosarcoma Cells." Molecular Medicine Reports, vol. 10, no. 6, 2014, pp. 2985-92.
Feng T, Qiao G, Feng L, et al. Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells. Mol Med Rep. 2014;10(6):2985-92.
Feng, T., Qiao, G., Feng, L., Qi, W., Huang, Y., Yao, Y., & Shen, Z. (2014). Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells. Molecular Medicine Reports, 10(6), 2985-92. https://doi.org/10.3892/mmr.2014.2618
Feng T, et al. Stathmin Is Key in Reversion of Doxorubicin Resistance By Arsenic Trioxide in Osteosarcoma Cells. Mol Med Rep. 2014;10(6):2985-92. PubMed PMID: 25310700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells. AU - Feng,Tao, AU - Qiao,Guanglei, AU - Feng,Li, AU - Qi,Weixiang, AU - Huang,Yujing, AU - Yao,Yang, AU - Shen,Zan, Y1 - 2014/10/09/ PY - 2013/12/02/received PY - 2014/06/26/accepted PY - 2014/10/14/entrez PY - 2014/10/14/pubmed PY - 2015/6/20/medline SP - 2985 EP - 92 JF - Molecular medicine reports JO - Mol Med Rep VL - 10 IS - 6 N2 - 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. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/25310700/Stathmin_is_key_in_reversion_of_doxorubicin_resistance_by_arsenic_trioxide_in_osteosarcoma_cells_ L2 - http://www.spandidos-publications.com/mmr/10/6/2985 DB - PRIME DP - Unbound Medicine ER -