Selective death of human breast cancer cells by lytic immunoliposomes: Correlation with their HER2 expression level.
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.
Barrajón-Catalán
Enrique
E
Molecular and Cellular Biology Institute, Miguel Hernández University, Alicante, Spain.
Menéndez-Gutiérrez
María P
MP
Falco
Alberto
A
Carrato
Alfredo
A
Saceda
Miguel
M
Micol
Vicente
V
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008081:Liposomes; D008555:Melitten / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008081:Liposomes; D008555:Melitten; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab