Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level

Cancer Lett. 2010 Apr 28;290(2):192-203. doi: 10.1016/j.canlet.2009.09.010. Epub 2009 Nov 5.

Abstract

Trastuzumab (Herceptin) targets the human epidermal growth factor receptor 2 (HER2), which is overexpressed in 20-30% of breast and ovarian cancers carrying a bad prognosis. Our purpose was to target HER2-overexpressing human breast cancer cells with pegylated immunoliposomes bearing trastuzumab and containing melittin, which has recently shown anticancer properties. Using a panel of human breast cancer cells with different HER2 expression levels, these immunoliposomes decreased cancer cells viability in a dose-response manner and in correlation to their level of HER2 expression. Specific binding of the immunoliposomes to SKBr3 breast cancer cells was shown by ImageStream-based analysis. The morphological changes observed in the treated cells suggested a cytolytic process. This preclinical approach may suppose an effective strategy for the treatment of HER2-overexpressing tumors, and can support the development of an early phases I-II clinical trial. Trastuzumab resistant breast cancer cells (JIMT-1), can also be targeted using this approach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / administration & dosage*
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Separation
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Drug Delivery Systems / methods*
  • Female
  • Flow Cytometry
  • Humans
  • Image Processing, Computer-Assisted
  • Liposomes
  • Melitten / administration & dosage*
  • Receptor, ErbB-2 / biosynthesis*
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Liposomes
  • Melitten
  • Receptor, ErbB-2
  • Trastuzumab