A novel LMP1 antibody synergizes with mitomycin C to inhibit nasopharyngeal carcinoma growth in vivo through inducing apoptosis and downregulating vascular endothelial growth factor

Int J Mol Sci. 2012;13(2):2208-2218. doi: 10.3390/ijms13022208. Epub 2012 Feb 17.

Abstract

Combined therapy emerges as an attractive strategy for cancer treatment. The aim of this study was to investigate the inhibitory effects of mitomycin C (MMC) combined with a novel antibody fragment (Fab) targeting latent membrane protein 1 (LMP1) on nasopharyngeal carcinoma (NPC) xenograft nude mice. The inhibitory rates of MMC (2 mg/kg), Fab (4 mg/kg), MMC (2 mg/kg) + Fab (4 mg/kg), and MMC (1 mg/kg) + Fab (4 mg/kg) were 20.1%, 7.3%, 42.5% and 40.5%, respectively. Flow cytometry analysis showed that the apoptotic rate of xenograft tumor cells in the MMC and Fab combination group was 28 ± 4.12%, significantly higher than the MMC (2 mg/kg) group (P < 0.01). Immunohistochemical staining showed that VEGF expression in NPC xenografts was significantly inhibited in the combination group compared to the Fab (4 mg/kg) group (P < 0.05). In conclusion, both MMC and Fab could inhibit NPC xenograft tumor growth in vivo and combination therapy showed apparent synergistic anti-tumor effects, which may be due to the induction of tumor cell apoptosis and the downregulation of VEGF expression. These results suggest that the novel combined therapy utilizing traditional chemotherapeutics and antibody-targeted therapy could be a promising strategy for the treatment of NPC.

Keywords: VEGF; antibody targeted therapy; apoptosis; latent membrane protein 1; mitomycin C; nasopharyngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Down-Regulation / drug effects
  • Drug Synergism
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitomycin / pharmacology*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / metabolism
  • Viral Matrix Proteins / antagonists & inhibitors
  • Viral Matrix Proteins / immunology*
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Vascular Endothelial Growth Factor A
  • Viral Matrix Proteins
  • Mitomycin