title: EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo.
abstract: Nimotuzumab is shown to be efficacious in advanced pancreatic cancer treatment, but its predictive marker has not been established.
  
  
  
  To investigate the impact of EGFR and KRAS status on antitumor efficacy of nimotuzumab and to explore its underlying mechanism.
  
  
  
  EGFR expressions of pancreatic cancer cell lines, BxPC3, Panc-1, and Patu-8988, were analyzed by Western blot and immunocytochemistry, and KRAS status was determined by gene sequencing. Anti-tumor effect of nimotuzumab were evaluated in vitro and in vivo. The expressions of related molecules in EGFR pathway and IL-6 was analyzed by Western blot, immunohistochemistry, and/or real-time PCR.
  
  
  
  BxPC3 cells had wild type KRAS and high-level EGFR; Panc-1 cells had mutant KRAS (G13A) and low-level EGFR; Patu-8988 cells had mutant KRAS (G12V) and high-level EGFR. Nimotuzumab did not affect cell proliferation or apoptosis in vitro. Growth of BxPC3 and Patu-8988 xenografts were significantly inhibited by nimotuzumab, but not Panc-1 xenografts, compared with that of the control group. Expression of EGFR in BxPC3 and Patu-8988 xenografts was significantly reduced by nimotuzumab. The IL-6 expression in BxPC3 and Patu-8988 xenografts was higher than that in Panc-1 xenografts in the control group, and was significantly reduced by nimotuzumab.
  
  
  
  Pancreatic cancer cells with EGFR high expression were more sensitive to nimotuzumab in vivo. KRAS status had no impact on anti-tumor efficacy of nimotuzumab in pancreatic cancer cells.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Zhou
authors.forename: Liangjun
authors.initials: L
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.forename: Fangmi
authors.initials: F
authors.lastname: Ding
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Qu
authors.initials: Q
authors.lastname: Cai
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Oncology, RuiJin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijiner Road, Shanghai 200025, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C508600:IL6 protein, human; D015850:Interleukin-6; C117307:KRAS protein, human; C501466:nimotuzumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)