Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level |
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Authors: | Enrique Barrajó n-Catalá n,Marí a P. Mené ndez-Gutié rrez,Alberto Falco,Alfredo Carrato,Miguel Saceda,Vicente Micol |
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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 |
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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. |
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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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