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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 | 27-Ald-triterpenoid saponins from Adina rubella显示文摘Four new triterpenoid saponins were isolated from the roots of Adina rubella Hance. They were characterized as adinaic acid 3β-O-[α-L-rhamnopyranosyl(l→2)-β-D-glucopyranosyl(l→2)-β-D-glucurono-pyranoside-6-O-methyl ester]-28-O-β-D)-glucopyranoside, adinaic acid 3β-O-[α-L-rham-nopyranosyl(l→2)-β-D-glucopyranosyl(l→2)-β-D-glucuronopyranoside-6-O-butyl ester]-28-O-β-D-glu-copyranoside, adinaic acid 3β-O-[β-D-glucopyranosyl(l→2)-β-D-glucopyranosyl]-(28→1)-β-D-gluco-pyranosyl(l→6)-β-D-glucopyranosyl ester, 27-hydroxyursolic acid 3β-O-[α-L-rhamnopyranosyl (l→2)-β-O-glucopyranosyl(l→2)-β-D)-glucuronopyranoside-6-O-methyl ester]-28-O-β-D)-glucopyranoside. Their structures were elucidated by spectral methods, especially with the aid of 2D NMR techniques. Their complete assignments of the 1H and 13C NMR signals were carried out. | Fan, GJ He, ZS Wu, HM Xu, JF | 1997 | Chinese Journal of Chemistry1997，15，5： | 2 |
| 3 | Therapeutic approaches for ischemia/reperfusion injury in the liver 显示文摘 | Fan C Zwacka RM Engelhardt JF | 1999 | J Mol Med (Berl)1999，77，8： | 1 |
| 4 | Site-directed antisense oligonucleoti- de decreases the expression of amyloid precursor protein and reverses def- icits in learning and memory in aged SAMP8 mice显示文摘 | Kumar VB Fan' SA Flood JF | 2000 | Peptides2000，21，12： | 1 |
| 5 | Temporal pattern of NFkBactivation influences apoptotic cell fate in a stimuli -dependentfashion 显示文摘 | Fan C Yang J Engelhardt JF | 2002 | J Cell Sci2002，115，24： | 1 |
| 6 | Therapeutic approaches for ischemia/reperfusion injury in the liver显示文摘 | Fan C Zwacka RM Engelhardt JF | 1999 | J Mol Med1999，77，8： | 1 |
| 7 | The estimation of sam- ple size in multi-stage sampling and its application in medical survey 显示文摘 | Wang JF Gao G Fan YB | 2006 | Appl Math Comput2006，178，： | 1 |
| 8 | Gene expression in lingual mucous membranes with common tongue coatings obtained from cancer patients 显示文摘 | Zhang JF Fan Y Hao JF | 2008 | Journal of Chinese Clinical Medicine2008，3，6： | 1 |
| 9 | Genetic polymorphisms of TLR3 are associated with Nasopharyngeal carcinoma risk in Cantonese population显示文摘 | He JF Jia WH Fan Q | 2007 | BMC Cancer2007，7，： | 1 |
| 10 | Laparoscopie treatment of severe acute pancreatitis显示文摘 | Zhu JF Fan XH Zhang XH | 2001 | Surg Endosc2001，15，2： | 1 |
| 11 | Survival after hypocalcemia, hypo-magnesemia, hypokalemia and cardiac arrest following mildhydrofluoric acid burn显示文摘 | Wu ML Deng JF Fan JS | 2010 | Clin Toxicol ( Phila)2010，48，9： | 1 |
| 12 | Survival after hypocalcemia,hypomagnesemia,hypokalemia and cardiac arrest following mild hydrofluoric acid burn显示文摘 | Wu ML Deng JF Fan JS | 2010 | Clin Toxicol (Phila)2010，48，9： | 1 |
| 13 | Genetic polymorphisms of TLR3 are associated with nasopharyngeal carcinoma risk in Cantonese population显示文摘 | He JF Jia WH Fan Q | 2007 | BMC Cancer2007，7，： | 1 |
| 14 | Antioxidant effects and cytotoxicity of three purified polysaccharides from Ligusticum chuanxiong Hort显示文摘 | YUAN JF ZHANG ZQ FAN ZC | | 0，，04： | 1 |
| 15 | Recombination of humancoxsackievirus B5 in hand,foot,and mouth disease patients,China显示文摘 | Han JF Jiang T Fan XL | 2012 | Emerg Infect Dis2012，18，2： | 1 |
| 16 | Preparation and Characterization of Poly (butylene terephthalate) Nanocomposites from Thermally Stable Organic - modified Montmorillonite显示文摘 | Xiao JF Hu Y Wang ZZ Tong Y Chen ZY Fan WC | 2005 | Eur Polym J2005，41，： | 1 |
| 17 | lnhibitory effect of melanoma differentiation associated gene-7/interleukin-24 on invasion in vitro of human melanoma cancer cells 显示文摘 | lin BW Jiao ZL Fan JF | 2013 | Korean Med Sci2013，28，6： | 1 |
| 18 | A study of aortic dimension in type B aortic dissection显示文摘 | Xu SD Huang FJ Du JH Li Y Fan ZM Yang JF | 2008 | Interact Cardiovasc Thorac Surg2008，7，： | 1 |
| 19 | Antioxidant effects and cytotoxicity of three purified polysaccharides from Ligusticum chuanxiong Hort显示文摘 | Yuan JF Zhang ZQ Fan ZC | | 0，，： | 1 |
| 20 | Effects of drying method on physicochemical and functional properties of soy protein isolates 显示文摘 | Hu XZ Cheng YQ Fan JF | 2010 | Journal of Food Processing and Preservation2010，34，： | 1 |
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