title: Inhibition of the JAK2/STAT3 signaling pathway exerts a therapeutic effect on osteosarcoma.
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.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Qianliang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Zou
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Schwartz
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Fuchs
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Zugen
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C548902:FLLL 32; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D003474:Curcumin