Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in osteosarcoma, and hence, may serve as a therapeutic target. In order to target STAT3, we tested two new STAT3 inhibitors, LLL12 and FLLL32. LLL12 and FLLL32 inhibit STAT3 phosphorylation and STAT3 downstream targets. LLL12 and FLLL32 also inhibit IL-6 induced STAT3 phosphorylation. The inhibition of STAT3 by LLL12 and FLLL32 resulted in the induction of apoptosis, reduction of plating efficiency, and migration in osteosarcoma cells. Furthermore, LLL12 and FLLL32 inhibited SJSA osteosarcoma cells and OS-33 tumor growth in murine xenografts. These results provide evidence that constitutive STAT3 signaling is required for osteosarcoma survival and migration in vitro and tumor growth in vivo. Blocking persistent STAT3 signaling by LLL12 and FLLL32 may be a novel therapeutic approach for osteosarcoma.
基金：
Ohio State University Comprehensive Cancer Center; Hematology and Oncology Department at the Nationwide Children's Hospital
第一作者单位：[6]Ohio State Univ, Dept Pediat, Coll Med, Columbus, OH 43210 USA
通讯作者：
通讯机构：[1]Nationwide Childrens Hosp, Dept Pediat, Ctr Childhood Canc, Res Inst, Columbus, OH 43205 USA[6]Ohio State Univ, Dept Pediat, Coll Med, Columbus, OH 43210 USA[*1]Nationwide Childrens Hosp, Dept Pediat, Ctr Childhood Canc, Res Inst, 700 Childrens Dr, Columbus, OH 43205 USA
推荐引用方式(GB/T 7714)：
Onimoe Grace-Ifeyinwa,Liu Aiguo,Lin Li,et al.Small molecules, LLL12 and FLLL32, inhibit STAT3 and exhibit potent growth suppressive activity in osteosarcoma cells and tumor growth in mice[J].INVESTIGATIONAL NEW DRUGS.2012,30(3):916-926.doi:10.1007/s10637-011-9645-1.
APA：
Onimoe, Grace-Ifeyinwa,Liu, Aiguo,Lin, Li,Wei, Chang-Ching,Schwartz, Eric B....&Lin, Jiayuh.(2012).Small molecules, LLL12 and FLLL32, inhibit STAT3 and exhibit potent growth suppressive activity in osteosarcoma cells and tumor growth in mice.INVESTIGATIONAL NEW DRUGS,30,(3)
MLA：
Onimoe, Grace-Ifeyinwa,et al."Small molecules, LLL12 and FLLL32, inhibit STAT3 and exhibit potent growth suppressive activity in osteosarcoma cells and tumor growth in mice".INVESTIGATIONAL NEW DRUGS 30..3(2012):916-926
