Trabectedin suppresses osteosarcoma pulmonary metastasis in a mouse tumor xenograft model

被引:1
作者
Inoue, Masahiro [1 ]
Horiuchi, Keisuke [1 ,2 ]
Susa, Michiro [1 ]
Taguchi, Eiko [1 ]
Ishizaka, Takahiro [1 ]
Rikitake, Hajime [1 ]
Matsuhashi, Yusuke [1 ]
Chiba, Kazuhiro [1 ]
机构
[1] Natl Def Med Coll, Dept Orthoped Surg, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan
[2] Keio Univ, Dept Orthoped Surg, Sch Med, Tokyo, Japan
关键词
ERK-MAP kinase; osteosarcoma; pulmonary metastasis; trabectedin; EFFECTIVE COMBINATION; PHASE-II; ECTEINASCIDIN-743; CHEMOTHERAPY; ANTITUMOR; SARCOMA; LIPOSARCOMA; MECHANISM; EFFICACY; ET-743;
D O I
10.1002/jor.25105
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Osteosarcoma (OS) is the most common primary bone tumor that mainly affects adolescents and young adults. Although standard treatment modality can achieve up to 60%-70% 5-year survival rate, there has not been any substantial improvement over the past four decades. Furthermore, those presenting with pulmonary metastatic lesions often undergo a highly unfavorable clinical course. Therefore, there is a severely unmet clinical need to provide a more effective treatment for patients with OS. In this study, we show that trabectedin (TBD), a chemotherapeutic agent approved for soft tissue sarcomas, significantly suppresses pulmonary metastasis in a mouse OS xenograft model. In vitro experiments revealed that TBD suppresses cell migration potentially by downregulating the activity of ERK1/2, intracellular molecules that are critically involved in the regulation of cell motility. Collectively, our data may provide a basis for further investigation of TBD on the potential use for OS patients who are at great risk of pulmonary metastasis.
引用
收藏
页码:945 / 953
页数:9
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