title: An investigation of the effect of sorafenib on tumour growth and recurrence after liver cancer resection in nude mice independent of phosphorylated extracellular signal-regulated kinase levels.
abstract: OBJECTIVE
  The goal of this study is to investigate the effects of sorafenib on tumor growth, recurrence and metastasis after curative resection of liver cancer.
  
  
  METHODS
  SMMC-7721 and HCCLM3 liver tumors, each with different metastatic potential and basal phosphorylated extracellular signal-regulated kinase (pERK) levels, were orthotopically implanted into 56 nude mice. Mice were divided into a treatment sub study and a prevention sub study.
  
  
  RESULTS
  In the treatment sub study, tumor volumes in the high pERK-expressing HCCLM3 model were 2.58 ? 0.83 and 0.38 ? 0.09 cm(3) without and with sorafenib, respectively (p < 0.001). The corresponding volumes in the low pERK-expressing SMMC-7721 model were 1.36 ? 0.24 and 0.24 ? 0.14 cm(3) (p < 0.001), respectively. Sorafenib inhibited HCCLM3 cell proliferation and decreased tumor angiogenesis, but did not inhibit proliferation in the SMMC-7721 model. In the prevention sub study, intrahepatic recurrent tumor volumes were 1.96 ? 0.45 and 0.18 ? 0.24 cm(3) (p < 0.001); lung metastasis frequencies were 100 and 0% (p = 0.005); and lifespans were 36 ? 3 and 46 ? 5 days (p = 0.002) in the control and sorafenib subgroups, respectively.
  
  
  CONCLUSIONS
  Sorafenib inhibits tumor growth and prevents metastatic recurrence after resection of hepatocellular carcinoma in nude mice. The effect of sorafenib does not exclusively depend on high levels of pERK in tumors.
authors.affiliation: Fudan University, Liver Cancer Institute and Zhongshan Hospital, Shanghai, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Xiao-Wu
authors.initials: XW
authors.lastname: Huang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Tan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases