Anti-HER-2 engineering antibody ChA21 inhibits growth and induces apoptosis of SK-OV-3 cells

J Exp Clin Cancer Res. 2010 Mar 10;29(1):23. doi: 10.1186/1756-9966-29-23.

Abstract

Background and aims: Anti-HER-2 antibodies targeting distinct epitopes have different biological functions on cancer cells. In a previous study, we demonstrated that anti-HER-2 engineering antibody ChA21 was able to bind to subdomain I of HER-2 extracellular domain. In this study, The effects of ChA21 on growth and apoptosis against ovarian carcinoma cell SK-OV-3 over-expressing HER-2 in vitro and in vivo were investigated.

Methods: Cell growth inhibition was evaluated by MTT assay. Apoptosis was detected by TUNEL stain, transmission electron microscopy and flow cytometry on cultured cells and tissue sections from nude mice xenografts. The apoptosis-related proteins Bax and Bcl-2 were assessed by immunohistochemistry.

Results: We found that treatment of ChA21 caused a dose-dependent decrease of cell proliferation in vitro and a significant inhibition of tumor growth in vivo. ChA21 therapy led to a significant increase in the induction of apoptosis, and up-regulated the expression of Bax, while the expression of Bcl-2 was down-regulated.

Conclusion: These data suggest that ChA21 inhibits the growth and induces apoptosis of SK-OV-3 via regulating the balance between Bax and Bcl-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antibodies, Monoclonal / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptor, ErbB-2 / immunology*
  • Recombinant Fusion Proteins / pharmacology*
  • Single-Chain Antibodies / pharmacology*
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • Single-Chain Antibodies
  • bcl-2-Associated X Protein
  • Receptor, ErbB-2