|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 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 | The discovery of eclogite dikes in low-greenschist facies volcaniclastic rocks of the Dabie Mountains显示文摘ECLOGITE occurs in different metamorphic rocks in the Dabie Mountains. Some dike-likeeclogite and garnet amphibolite were discovered when we investigated the newly founded low-greenschist facies volcaniclastic rocks in Changpu, Yuexi County and Siqian, Taihu County(fig.1). Coesite and quartz pseudomorphs exist in garnet and omphacite. By studying the oc-currence and petrography-mineralogy characteristic, we believe that the eclogite is of | Gao, TS Tang, JF Zhou, CT Hou, MJ Qian, CC | 1997 | Chinese Science Bulletin1997，42，20： | 3 |
| 3 | Bcl2 inhibits abasie site repair by down-regulating APE1 endonuclease activity 显示文摘 | ZHAO JF GAO FQ ZHANG YD | 2008 | J Biol Chem2008，283，15： | 1 |
| 4 | Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat live transplantation显示文摘 | Gao W Bentley RC Madden JF | 1998 | Hepatology1998，27，6： | 1 |
| 5 | Analysis of microsatellites in major crops assessed by computational and experimental approaches显示文摘 | Gao LF Tang JF Li HW | 2003 | Molecular Breeding2003，12，3： | 1 |
| 6 | The effect of therapeutic mild hypothermia on genomics of the hippocampus following moderate traumatic brain injury in rats 显示文摘 | Feng JF Zhang KM Gao GY | 2010 | Neurosurgery2010，67，3： | 1 |
| 7 | A ligand exchange route to highly luminescent surface-functionalized ZoS nanoparticles and their transparent polymer nanocomposites显示文摘 | Lv CL Gao JF Fu YQ | | 0，，： | 1 |
| 8 | P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration显示文摘 | Feng JF Gao XF Pu YY | 2015 | Purinergic Signal2015，11，3： | 1 |
| 9 | Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent显示文摘 | Camargo CA Madden JF Gao W | 1997 | Hepatology1997，26，6： | 1 |
| 10 | Epidemic characteristics ofhand,foot,and mouth disease in Shanghai from 2009to2010:Enterovirus 71subgenotype C4as the primary causa-tive agent and a high incidence of mixed infections with cox-sackievirus A16显示文摘 | Yan XF Gao S Xia JF | 2012 | Scand J Infect Dis2012，44，4： | 1 |
| 11 | Interleukin-6 protects against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent显示文摘 | Camargo CA Jr Madden JF Gao W | 1997 | Hepatology1997，26，： | 1 |
| 12 | Concomitant EGFR inhibitors combined with radiation for treatment of non-small cell lung carcinoma显示文摘 | Zheng D J Yu GH Gao JF | 2013 | Asian Pac J Cancer Prey2013，14，8： | 1 |
| 13 | 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 |
| 14 | Biological features of novel avian influenza A (H7N9) virus显示文摘 | Zhou JF Wang DY Gao RB | 2013 | Nature2013，499，7459： | 1 |
| 15 | Dual inhibition of the renin-angiotensin system in high-risk diabetes and risk for stroke and other outcomes:results of the ONTARGET trial显示文摘 | Mann JF Anderson C Gao P | | 0，，02： | 1 |
| 16 | Regulation of antigen-express- ing dendritic cells by double negative regulatory T cells 显示文摘 | Gao JF Mclntyre MS Juvet SC | 2011 | Eur J Im- munol2011，41，9： | 1 |
| 17 | Angiolymphoid hyperplasia with eosinophilia affecting the scrotum: a rare case report with molecular evidence显示文摘 | Chen JF Gao HW Wu BY | 2010 | J Dermatol2010，37，4： | 1 |
| 18 | Epidemic characteristics of hand, foot, and mouth disease in Shanghai from 2009 to 2010: Enterovirus 71 subgenotype C4 as the primary causative agent and a high incidence of mixed infections with coxsackievirus A16 显示文摘 | Yan XF Gao S Xia JF | 2012 | Scandinavian Journal of Infectious Diseases2012，44，4： | 1 |
| 19 | Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation显示文摘 | Gao W Bentley RC Madden JF Clavien PA | 1998 | Hepatology1998，27，： | 1 |
| 20 | Synthesis, assembly, and intracellular transport of the platelet glycoprotein Ib - IX - V complex 显示文摘 | Dong JF Gao S Lopez JA | 1998 | J Biol Chem1998，273，31： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员