Inhibition of the JAK2/STAT3 signaling pathway exerts a therapeutic effect on osteosarcoma

Yan,Jun; Wang,Qianliang; Zou,Kang; Wang,Li; Schwartz,Eric B.; Fuchs,James  R.; Zheng,Zugen; Wu,Jianqiang

doi:10.3892/mmr.2015.3439

Inhibition of the JAK2/STAT3 signaling pathway exerts a therapeutic effect on osteosarcoma

Authors:
- Jun Yan
- Qianliang Wang
- Kang Zou
- Li Wang
- Eric B. Schwartz
- James R. Fuchs
- Zugen Zheng
- Jianqiang Wu
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Affiliations: 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, Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Research Foundation, Cincinnati Children's Hospital University of Cincinnati, Cincinnati, OH 45229, USA
Published online on: March 5, 2015 https://doi.org/10.3892/mmr.2015.3439
Pages: 498-502

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Abstract

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.

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