Yan Jun, Wang Qianliang, Zou Kang, Wang Li, Schwartz Eric B, Fuchs James R, Zheng Zugen, Wu Jianqiang
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
Mol Med Rep. 2015 Jul;12(1):498-502. doi: 10.3892/mmr.2015.3439. Epub 2015 Mar 5.
Osteosarcoma (OS) is the most common type of malignant bone tumor. Despite aggressive multimodal treatments, including surgical resection, chemotherapy and adjunctive immunotherapies, patients with OS with high-grade malignancy have a poor five-year survival rate that has remained unchanged over the past two decades, highlighting the urgent requirement for novel therapeutic approaches. Signal transducers and activators of transcription 3 (STAT3) has been implicated as an oncogene and therapeutic target in a variety of neoplastic diseases. The aim of the present study was to determine whether inhibition of the janus kinase 2 (JAK2)/STAT3 pathway by FLLL32, a specific JAK2/STAT3 inhibitor, is able to provide a potential therapy for OS. FLLL32 inhibited OS cell growth in vitro and delayed OS growth in an OS xenograft nude mouse model. STAT3 knockdown by short hairpin RNA delayed OS formation in vivo. Thus, the JAK2/STAT3 pathway is important in OS formation. Efficacy of the FLLL32 pharmacological inhibitor in delaying OS growth suggests that targeting JAK2/STAT3 may be a potential therapeutic strategy for patients with OS.
骨肉瘤（OS）是最常见的恶性骨肿瘤类型。尽管采用了积极的多模式治疗，包括手术切除、化疗和辅助免疫疗法，但高度恶性的骨肉瘤患者的五年生存率仍然很低，在过去二十年中一直没有变化，这凸显了对新型治疗方法的迫切需求。信号转导子和转录激活子3（STAT3）在多种肿瘤性疾病中被认为是一种癌基因和治疗靶点。本研究的目的是确定特异性JAK2/STAT3抑制剂FLLL32对Janus激酶2（JAK2）/STAT3途径的抑制是否能够为骨肉瘤提供一种潜在的治疗方法。FLLL32在体外抑制骨肉瘤细胞生长，并在骨肉瘤异种移植裸鼠模型中延缓骨肉瘤生长。短发夹RNA敲低STAT3可在体内延缓骨肉瘤形成。因此，JAK2/STAT3途径在骨肉瘤形成中很重要。FLLL32药理抑制剂在延缓骨肉瘤生长方面的疗效表明，靶向JAK2/STAT3可能是骨肉瘤患者的一种潜在治疗策略。
