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| 1 | Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3显示文摘AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC).METHODS: Human and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model.RESULTS: Sorafenib decreased STAT3 phosphorylationat the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phosphatase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib signifi cantly inhibited STAT3 activity, reducing tumor growth and metastasis.CONCLUSION: Sorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation. | Fang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian ZhouFang-Ming Gu, Quan-Lin Li, Qiang Gao, Jia-Hao Jiang, Xiao-Yong Huang, Jin-Feng Pan, Jia Fan, Jian Zhou, Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai 200032, China Author contributions: Gu FM, Li QL and Gao Q contributed equally to this work Gu FM and Li QL performed the experi- ments and interpretation of the data and statistical analysis Zhou J and Gao Q contributed to the conception and design of the study Gu FM, Gao Q, Li QL and Zhou J wrote the manuscript Jiang JH, Huang XY, Pan JF and Fan J made substantial contri- bution to the design and conception of the study and interpreta- tion of data all authors read and approved the f inal manuscript. | 2011 | World Journal of Gastroenterology2011，17，34： | 18 |
| 2 | 母亲妊娠期焦虑抑郁对孩子应激性心率及血压的影响显示文摘心理障碍,包括焦虑和抑郁在妊娠期间十分常见。该研究目的在于确定母亲的这些心理障碍是否会对后代的心血管反应产生影响。方法:对231名孕妇的心理状态进行评定,在其后代(n=216)7~9岁时进行视频压力反应测试。测定静息时、观看压力视频时和恢复期的心率及血压水平。 | 刘莉 叶鹏 Fan F Zou Y Tian H Zhang Y Zhang J Ma X Meng Y Yue Y Liu K Dart AM | 2015 | 中华高血压杂志2015，23，6： | 5 |
| 3 | Insights into human CD34(+) hematopoietic stem/progenitor cells through a systematically proteomic survey coupled with transcriptome显示文摘 | Liu F Lu J Fan HH Wang ZQ Cui SJ Zhang GA Chi M Zhang X Yang PY Chen Z Han ZG | 2006 | 中国生物学文摘2006，20，5： | 2 |
| 4 | Spectral sensitization of the heterogeneous photocatalytic oxidation of hydroquinone in aqueous solutions at phthalocyanine - coated titanium dioxide powders显示文摘 | Fu - Ren F Fan Allen J Bard | 1979 | J Am Chem Soc1979，101，20： | 1 |
| 5 | Geochemistry of Mesozoic mafic rocks adjacent to the Chenzhou-Linwu fault, South China:Implications for the lithospheric boundary between the Yangtze and Cathaysia blocks显示文摘 | Wang Y J Fan W M Guo F | 2003 | Int Geol Rev2003，45，3： | 1 |
| 6 | 查看详情显示文摘 | Fan H Xu X F Niu X J | | 0，，： | 1 |
| 7 | Adsorption of single Li and the formation of small Li clusters on graphene for the anode of lithium-ion batteries 显示文摘 | FAN X F ZHENG W T KOU J L | 2013 | ACS Applied Materials And Inter- faces2013，16，5： | 1 |
| 8 | Prediction of texture char- acteristics from extrusion food surface images using a computer vision system and artificial neural networks 显示文摘 | Fan F H Ma Q Ge J | 2013 | Journal of Food Engineering2013，118，： | 1 |
| 9 | The epidemiology of silent brain infarction:a systematic review of population - based co- horts 显示文摘 | Fanning J P Wang A A Fraser J F | 2014 | BMC Medicine2014，12，1： | 1 |
| 10 | Effect of Bi203 on physical, optical and structural properties of boron silicon bismuthate glasses 显示文摘 | GAO G HU L L FAN H Y WANG G N LI K F FENG S Y FAN S J CHEN H Y | 2009 | Optical Materials2009，32，： | 1 |
| 11 | Water-soluble triscy- clometalated organoiridium complex: phosphorescent nan- oparticle formation, nonlinear optics, and application for cell imaging显示文摘 | Fan Y P Zhao J Y Yan Q F | 2014 | ACS Appl Mater Interfaces2014，6，： | 1 |
| 12 | Late Mesozoic calcalka- line volcanism ot' post-orogenic extension in the northern Da Hinggan Mountains, Northeastern China显示文摘 | Fan W M Guo F Wang Y J | 2003 | Journal of Vol canology and Geothermal Research2003，121，： | 1 |
| 13 | The TIL commissioning and performance显示文摘 | X Zhang W Zheng X Wei F Jing Z Sui K Zheng Q Xu X Yuan X Jiang L Yang P Ma M Li J Wang D Hu S He F Li Z Peng B Feng H Zhou L Guo X Li X Zhang J Su Q Zhu H Yu R Zhao C Ma H He D Fan W Zhang | 2008 | Journal of Physics: Conference Series2008，，3： | 1 |
| 14 | Elasto-plastic stability of sin- gle-layer reticulated domes with initial curvature of mem- bers显示文摘 | FAN F YAN J C CAO Z G | 2012 | Thin-Walled Structures2012，60，： | 1 |
| 15 | Image restoration combing a total variational filter and a fourth-order filter显示文摘 | LI F SHEN C M FAN J S | 2007 | Journal of Visual Communication and Image Representation2007，18，4： | 1 |
| 16 | Expression and purification of two different antimicrobial peptides, PR - 39 and Protegrin - 1 in Escherichia coli 显示文摘 | FAN F WU Y LIU J | 2010 | Protein Expr Purif2010，73，2： | 1 |
| 17 | Attentional phenotypesforthe analysis of higher mental function 显示文摘 | F sella J PosnerM Fan J etal | 2002 | The Scientific World Journal2002，2，24： | 1 |
| 18 | Natural variation in GS5 plays an important role in regulating grain size and yield in rice显示文摘 | Li Y B Fan C C Xing Y Z Jiang Y H Luo L J Sun L Shao D Xu C J Li X H Xiao J H He Y Q Zhang Q F | 2011 | Nature genetics2011，2，43： | 1 |
| 19 | When did the Emeishan mantle plume activity start? Geochronological and geochemical evidence from ultramafic-mafic dikes in southwestern China 显示文摘 | Guo F Fan W M Wang Y J Li C W | 2004 | International Geology Review2004，46，： | 1 |
| 20 | Transpedicular bone grafting following short-segment posterior instrumenta- tion for acute thoracolumbar burst fracture显示文摘 | Liao J C Fan K F Chen W J | 2009 | Orthope- dics2009，32，7： | 1 |
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