| 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 | A draft sequence of the rice (Oryza sativa ssp. indica) genome显示文摘The sequence of the rice genome holds fundamental information for its biology, including physiology, genetics, development, and evolution, as well as information on many beneficial phenotypes of economic significance. Using a 'whole genome shotgun' approach, we have pro-duced a draft rice genome sequence of Oryza sativa ssp. in-dica, the major crop rice subspecies in China and many other regions of Asia. The draft genome sequence is constructed from over 4.3 million successful sequencing traces with an accumulative total length of 2214.9 Mb. The initial assembly of the non-redundant sequences reached 409.76 Mb in length, based on 3.30 million successful sequencing traces with a total length of 1797.4 Mb from an indica variant cultivar 93-11, giving an estimated coverage of 95.29% of the rice genome with an average base accuracy of higher than 99%. The coverage of the draft sequence, the randomness of the sequence distribution, and the consistency of BIG-ASSEM-BLER, a custom-designed software package | YU Jun, HU Songnian, WANG Jun,LI Songgang WONG Ka-Shu Gane, LIU Bin,DENG Yajun, DAI Li, ZHOU Yan,ZHANG Xiuqing, CAO Mengliang, LIU Jing,SUN Jiandong , TANG Jiabin, CHEN Yanjiong,HUANG Xiaobing, LIN Wei, YE Chen, TONG Wei,CONG Lijuan, GENG Jianing, HAN Yujun, LI Lin,LI Wei, HU Guangqiang, HUANG Xiangang,LI Wenjie, LI Jian, LIU Zhanwei, LI Long,LIU Jianping, Ql Qiuhui, LIU Jinsong, LI Li,WANG Xuegang, LU Hong, WU Tingling,ZHU Miao, Nl Peixiang, HAN Hua, DONG Wei,REN Xiaoyu, FENG Xiaoli, GUI Peng,LI Xianran, WANG Hao, XU Xin, ZHAI Wenxue,XU Zhao, ZHANG Jinsong, HE Sijie,ZHANG Jianguo, XU Jichen, ZHANG Kunlin,ZHENG Xianwu, DONG Jianhai, ZENG Wanyong,TAO Lin, CHEN Xuewei, HE Jun, LIU Daofeng,TIAN Wei, TIAN Chaoguang, XIA Hongai,LI Gang, GAO Hui, LI Ping, CHEN Wei ,WANG Xudong, ZHANG Yong, HU Jianfei,WANG Jing, LIU Song, YANG Jian,ZHANG Guangyu, XIONG Yuqing, LI Zhijie,MAO Long, ZHOU Chengshu, ZHU Zhen,CHEN Runsheng, HAO Bailin,ZHENG Weimou, CHEN Shouyi, QUO Wei,LI Guojie, LIU Siqi, HUANG Guyang,TAO Ming, WANG Jian, ZHU Lihuang,YUAN Longping& YANG HuanmingBeijing Genomics Institute/Center of Genomics & Bioinformatics, Chinese Academy of Sciences, Beijing 101300, China Hangzhou Genomics Institute/Institute of Bioinformatics of Zhejiang University/Key Laboratory of Bioinformatics of Zhejiang Province, Hangzhou 310007, China Institute of Genetics, Chinese Academy of Sciences, Beijing 100101, China National Hybrid Rice R & D Center, Changsha 410125, China Laboratory of Bioinformatics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China College of Life Sciences, Peking University, Beijing 100871, China Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 1Q0080, China Digital China Ltd., Beijing 100080, China Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100080, China Medical College, Xi’an Jiaotong University, Xi’an 710061, ChinaThese authors contributed equally to this work.Corresponding author.Corresponden | 2001 | Chinese Science Bulletin2001，46，23： | 6 |
您所在的机构暂未开通此部分的功能，请联系管理员