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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 | Clinicopathologic study of primary intestinal B cell malignantlymphoma显示文摘 | Zhou Q Xu TR Fan QH Zhen ZX | 1999 | World Journal of Gastroenterology1999，5，6： | 6 |
| 3 | 笋芽顶端分生组织在竹秆横切面形态形成中的作用与机制研究显示文摘竹秆的横切面主要由表皮、皮层、维管组织、基本组织及髓腔(早期为髓组织)组成。这些组织均由笋芽茎顶端分生组织分化发育而来,且其在生长发育过程中促使了竹秆横切面形态(本文特指:竹秆横切面外轮廓形状、围度及壁-腔结构)的形成。然而,人们对于这一生长发育过程的生物学机制知之甚少。本研究利用解剖学、数学模拟等方法,对 20 种具不同秆径竹种的笋芽顶端分生组织进行了分析。研究结果发现,笋芽顶端分生组织指状形态的维持是竹子产生圆柱形竹秆的基础;在顶端分生组织细胞数目增加的同时,线性增加原体细胞数目应是竹子在演化过程中产生大径竹秆且保持规则壁-腔结构的方式。进一步通过研究一个竹壁增厚且壁-腔架构紊乱的稳定变异体———实肚竹( Phyllostachys nidularia f. farcta)发现,其笋芽顶端分生组织细胞数目减少且原体/原套细胞数比值降低使其产生了高比例的壁组分组织(指基本分生组织与肋状分生组织)与低比例的髓组织。上述 2 种组织的比例失衡,使得实肚竹笋芽在后续发育中壁组分组织随机挤入到了髓组织中,最终形成了实肚竹异常的竹秆横切面形态(竹壁多样化增厚且壁-腔结构紊乱)。此外,相对较小的顶端分生组织,使得实肚竹笋芽产生了较少的内源激素,如其生长素含量仅约为其原种篌竹的 67. 5%,各细胞分裂素含量也显著低于篌竹笋芽。转录组分析进一步发现,在实肚竹笋芽中与激素及代谢相关的功能基因呈显著下调表达。这些生理与分子变化最终导致了实肚竹竹秆矮化、秆径减小且生物量降低。本论文的研究结果为研究竹秆横切面发育提供了一个重要的视角,同时也为实肚竹厚壁茎秆的形成提出了一个合理的机制。 | Wang Y Sun X Ding Y Fei Z Jiao C Fan M Yao B Xin P Chu J Wei Q 王雨珺 魏强 | 2019 | 世界竹藤通讯2019，17，3： | 5 |
| 4 | Ikappa-Balpha and IkappaBbeta possess injury context-specific functions that uniquely influence hepatic NF-kappaB induction and inflammation显示文摘 | Fan C Li Q Zhang Y Liu X Luo M Abbott D | 2004 | J Clin Invest2004，113，： | 1 |
| 5 | TRPC6 Up-regulation in Ang Ⅱ-induced podocyte apoptosis might result from ERK activation and NF-kB translocation显示文摘 | Zhang H Ding J Fan Q | 2009 | Exp Biol Med2009，234，9： | 1 |
| 6 | Coating of carbon nanotube with nickel by electroless plating method显示文摘 | Li Q Fan S Han W | 1997 | Jpn J Appl Phys1997，36，： | 1 |
| 7 | An unmediated hydrogen peroxide biosensor based on hemoglobin incorporated in a montmorillonite membrane 显示文摘 | FAN C GAO Q ZHU D | 2001 | The Analyst2001，126，7： | 1 |
| 8 | Evaluation of the use of high CO2concentrations and cold storage to control Monilinia fructicola on sweet cherries显示文摘 | Tian S P Fan Q Xu Y | 2001 | Postharvest Biology and Technology2001，22，1： | 1 |
| 9 | Competition of crystalline and liquidcrystalline moieties in self-assembly of poly(oxyethylene)cholesterolethers显示文摘 | Xu J T Xue L Fan Z Q | 2006 | Macromolecules2006，39，8： | 1 |
| 10 | Synthesis and properties of polyurethane modifiedwith aminoethylaminopropyl poly(dimethyl siloxane) 显示文摘 | FAN Q L FANG J L CHEN Q M | 1999 | J Appl Polym Sci1999，74，： | 1 |
| 11 | Biologically active phenols from Saussurea medusa显示文摘 | FAN C Q YUE J M | 2003 | Bioorg Med Chem2003，11，5： | 1 |
| 12 | Aeta Mater显示文摘 | Fan D Chert L Q | 1997 | 45(2): 6111997，45，2： | 1 |
| 13 | Preparation and characterization of novel magnetic ZrO2/TiO2/Fe304 solid superacid 显示文摘 | Wang J Yang P P Fan M Q | 2007 | Mater Lett2007，61，1112： | 1 |
| 14 | Novel Sensitive high-throughput screening strategy for nitrilase-producing strains 显示文摘 | Zhu Q Fan A Wang Y S | 2007 | Applied and Enviromental Microbiology2007，73，19： | 1 |
| 15 | Variable selection via nonconcave penalized likelihood and its oracle properties显示文摘 | FAN J Q LI R Z | 2001 | Journal of the American Statistical Association2001，96，： | 1 |
| 16 | The mierostruetural evolu- tion of an Al-Zn-Mg-Cu during homogenization显示文摘 | FAN X JIANG D MENG Q | 2006 | Materials Let- ters2006，60，： | 1 |
| 17 | Adsorption of aflatoxin BI on montmorillonlte显示文摘 | Desheng Q Fan L Yanhu Y | 2005 | Poultry Science2005，84，6： | 1 |
| 18 | Kinetics of oxidation of total sulfite in the ammonia-based wet flue gas desulfurization process显示文摘 | JIA Y ZHONG Q FAN X Y | | 0，，： | 1 |
| 19 | A study of early pregnancy factor activity in preimplantation 显示文摘 | Fan X G Zheng Z Q | 1997 | Am J Reprod Immunol1997，37，5： | 1 |
| 20 | A new numerical method to simulate the non-Fourier heat conduction in a single-phase medium显示文摘 | Fan Q M Lu W Q | 2002 | Heat Mass Transfer2002，45，： | 1 |
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