Suppression of Signal Transducer and Activator of Transcription 3 Activation by Butein Inhibits Growth of Human Hepatocellular Carcinoma In Vivo

摘要: Purpose: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and third cause of global cancer mortality. Increasing evidence suggest that STAT3 a critical mediator oncogenic signaling in HCC controls expression several genes involved proliferation, survival, metastasis, angiogenesis. Thus, novel agents can suppress activation have potential for both prevention treatment HCC. Experimental Design: The effect butein on activation, associated protein kinases, STAT3-regulated gene products, cellular apoptosis was investigated. vivo growth human xenograft tumors male athymic nu/nu mice also examined. Results: We tested an agent, butein, its ability to cells nude model along with prospectively testing hypothesis inhibition virtual predictive functional proteomics tumor pathway technology platform. found inhibited constitutive inducible cells. suppression mediated through upstream kinases c-Src Janus-activated kinase 2. Butein proliferation significantly potentiated apoptotic effects paclitaxel doxorubicin When administered intraperitoneally, mice. Conclusions: Overall, cumulative results from experimental studies exerts antiproliferative proapoptotic vitro . Clin Cancer Res; 17(6); 1425–39. ©2010 AACR