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Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level
Authors:Enrique Barrajó  n-Catalá  n,Marí  a P. Mené  ndez-Gutié  rrez,Alberto Falco,Alfredo Carrato,Miguel Saceda,Vicente Micol
Affiliation:1. Molecular and Cellular Biology Institute (IBMC), Miguel Hernández University, Avda. de la Universidad s/n, E-03202 Elche, Alicante, Spain;2. Elche University Hospital, Biomedical Research Foundation (FIBElx), Camí de la Almazara 11, Ed. Anexo II, 03203 Elche, Alicante, Spain
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.
Keywords:HER2/neu HER2, human epidermal growth factor receptor 2   AbDR, lytic immunoliposomes with trastuzumab&trade     Mab, monoclonal antibody   AMP, antimicrobial peptide   PLA2, phospholipase 2   EYPC, egg yolk phosphatidylcholine   Chol, cholesterol   DSPE-PEG, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-2000   D2000   M, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide (PEG 2000)]   DR, lytic liposome (without antibody)   Rhod, Lissamine rhodamine dye   Rhod-PE, lissamine rhodamine B 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine   THIS, histidine buffered solution   Rhod-AbDR, rhodamine labeled AbDR   Rhod-DR, rhodamine labeled DR   HPLC, high performance liquid chromatography   AbDR-ø  , AbDR immunoliposome without lytic peptide   CC50, concentration corresponding to 50% cytotoxicity   PLD, phospholipase D   DAPI, 4&prime  ,6-diamidino-2-phenylindole dye
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