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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 | Solving surface plasmon resonances and near field in metallic nanostructures:Green’s matrix method and its applications显示文摘With the development of nanotechnology,many new optical phenomena in nanoscale have been demonstrated.Through the coupling of optical waves and collective oscillations of free electrons in metallic nanostructures,surface plasmon polaritons can be excited accompanying a strong near field enhancement that decays in a subwavelength scale,which have potential applications in the surface-enhanced Raman scattering,biosensor,optical communication,solar cells,and nonlinear optical frequency mixing.In the present article,we review the Green's matrix method for solving the surface plasmon resonances and near field in arbitrarily shaped nanostructures and in binary metallic nanostructures.Using this method,we design the plasmonic nanostructures whose resonances are tunable from the visible to near-infrared,study the interplay of plasmon resonances,and propose a new way to control plasmonic resonances in binary metallic nanostructures. | GU Ying LI Jia MARTIN Olivier J F GONG QiHuang | 2010 | Chinese Science Bulletin2010，55，24： | 3 |
| 3 | Electrically conductive epoxy resin composites containing polyaniline with different morphologies 显示文摘 | JIA Q M LI J B WANG L F | 2007 | Materials Science and Engineering A2007，448，： | 1 |
| 4 | Mechanism of gold and silver species on activated carbon显示文摘 | Jia Y F Steele J Hayward P | 1998 | Carbon1998，36，9： | 1 |
| 5 | Pharmacokinetic properties of hydroxysafflor yellow A in healthy Chinese female volunteers显示文摘 | Yang Z F Yang J Jia Y Y | 2009 | J Ethnopharmacol2009，124，3： | 1 |
| 6 | The structure and electronic property of BN nanotube 显示文摘 | Jia J F Wu H S Jiao H J | 2006 | Physica B2006，381，： | 1 |
| 7 | Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose显示文摘 | Jia D Y Liu H J Wang F W | 2008 | Neurosci Lett2008，440，1： | 1 |
| 8 | Visual acuity and quality of life outcomes in patients with cataract in Shuyi county,China显示文摘 | Zhao J L Sui R F Jia L J | 1998 | Am J Ophthalmol1998，126，： | 1 |
| 9 | Simple synthesis of hierarchically ordered mesocellular mesoporous silica materials hosting crosslinked enzyme aggregates 显示文摘 | Lee J Kim J Jia H F | 2005 | Small2005，1，7： | 1 |
| 10 | Biocompatibility of chitosan-coated iron oxide nanoparticles with osteoblast cells显示文摘 | Shi S F Jia J F Guo X K | 2012 | Int J Nanomedicine2012，7，： | 1 |
| 11 | Msophyll protoplasts from Solanum melongena var depressum bailey regenerate to fertile plants 显示文摘 | Jia J F Potrykus I | 1981 | Plant Cell Rep1981，1，： | 1 |
| 12 | Experimental investigation on the drying process of the sinter mixture显示文摘 | Dong H Jia F R Cai J J | 2012 | Powder Technology2012，218，： | 1 |
| 13 | Development and application of a new co-dominant PCR marker for detecting 1BL/ 1RS wheat rye chromosome translocations显示文摘 | CHAI J F ZHOU R H JIA J ZH | | 0，，： | 1 |
| 14 | The prevalence of dementia in urban and rural areas of China显示文摘 | Jia J Wang F Wei C | 2014 | Alzheimer''s Dement2014，10，1： | 1 |
| 15 | Identification of an endocytic signal essential for the antiviral action of IFITM3 显示文摘 | Jia R Xu F Qian J | 2014 | Cell Microbiol2014，16，7： | 1 |
| 16 | Activation of telomerase by human cytomegalovirus 显示文摘 | Strt K Liu C Rahbar A Zhu Q Liu L Wolmer- Solberg N Lou F Liu Z Shen J Jia J Kyo S Bj6rkholm M Sj6berg J S6derberg-Naucl6r C Xu D | 2009 | J Natl Cancer Inst2009，101，7： | 1 |
| 17 | Influence of retrogression temperature and time on the mechanical properties and exfoliation corrosion behavior of aluminium alloy AA7150显示文摘 | LI J F BIRBILIS N LI C X JIA Z Q CAI B ZHENG Z Q | 2009 | Materials Characterization2009，60，11： | 1 |
| 18 | Biological markers and their carbon isotopes as an approach to the paleoenvironmental reconstruction of Nansha area, South China Sea, during the last 30ka 显示文摘 | HU J F PENG P G JIA G D | 2002 | Organic Geochemistry2002，33，10： | 1 |
| 19 | Non-linear Principal Component Analysis with Application to Process Fault Detection显示文摘 | JIA F MARTIN E B MORRIS A J | 2000 | International Journal of System Science2000，31，11： | 1 |
| 20 | Heterologous expression of the chrysanthemum R2R3-MYB transcription factor CmMYB2 en- hances drought and salinity tolerance, increases hypersensitivity to ABA and delays flowering in arabidopsis thaliana显示文摘 | Hong S Su M C Jia F J | 2012 | Molec- ular Biotechnology2012，51，2： | 1 |
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