Antitumor activity of the novel human cytokine AIMP1 in an in vivo tumor model

Mol Cells. 2006 Apr 30;21(2):213-7.

Abstract

Although AIMP1 (previously known as p43) is one of three auxiliary proteins bound to a macromolecular aminoacyl tRNA complex, it is also secreted as a cytokine controlling both angiogenesis and immune responses. Here we show that systemically administered purified recombinant human AIMP1 had anti-tumor activity in mouse xenograft models. In Meth A-bearing Balb/c mice, tumor volume increased about 28 fold in the vehicle treatment group, while an increase of about 16.7 fold was observed in the AIMP1-treated group. We also evaluated the anti-tumor activity of AIMP1 in combination with a sub-clinical dose of the cytotoxic anti-tumor drug, paclitaxel. The growth of NUGC-3 human stomach cancer cells was suppressed by 84% and 94% by the combinations of 5 mg/kg paclitaxel + 25 mg/kg AIMP1 (p = 0.03), and 5 mg/kg paclitaxel + 50 mg/kg AIMP1 (p = 0.02), respectively, while 5 mg/kg paclitaxel alone suppressed growth by only 54% (p = 0.02). A similar cooperative effect of AIMP1 and paclitaxel was observed in a lung cancer xenograft model. These results suggest that AIMP1 may be useful as a novel anti-tumor agent.

MeSH terms

  • Animals
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / metabolism*
  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Histocompatibility Antigens / metabolism
  • Humans
  • Lung Neoplasms
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Paclitaxel / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Stomach Neoplasms
  • Transplantation, Heterologous

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Cytokines
  • Histocompatibility Antigens
  • Neoplasm Proteins
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • small inducible cytokine subfamily E, member 1
  • tumor-associated transplantation antigen
  • Paclitaxel