title: Stathmin is key in reversion of doxorubicin resistance by arsenic trioxide in osteosarcoma cells.
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.affiliation: Department of Oncology, Affiliated People's 6th Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: Department of Oncology, Affiliated People's 6th Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China.
authors.forename: Guanglei
authors.initials: G
authors.lastname: Qiao
authors.affiliation: Department of Pharmacy, The Donggang People's Hospital, Rizhao, Shandong 276800, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Oncology, Affiliated People's 6th Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China.
authors.forename: Weixiang
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Oncology, Affiliated People's 6th Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Oncology, Affiliated People's 6th Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Oncology, Affiliated People's 6th Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy*; D010087:Oxides / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D050777:Stathmin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D034741:RNA, Small Interfering; D050777:Stathmin; D004317:Doxorubicin; D000077237:Arsenic Trioxide