Combined treatment of human MCF-7 breast carcinoma with antibody, cationic lipid and hyaluronic acid using ex vivo assays.
The effective targeting of malignant cell surface antigens is essential in cancer therapy. Resistance to treatment and rapid invasion of cancer cells are the main causes of cancer mortality. Despite intense research efforts, treatments often have demonstrated insufficient outcomes in clinical applications. The aim of the present study was to determine whether combined administration of monoclonal antibody (Herceptin, trastuzumab) and anti-HER-2 (clone CB11) with hyaluronic acid (HA) and lipoplex (containing lipofectamine (LipA) and plasmid DNA) can produce a synergistic reaction to increase the therapeutic effect of monoclonal antibodies. To assess the treatment response, we cultured a 3-D MCF-7 cell line overexpressing HER-2 and CD44 receptors. The high density 3-D cell aggregation in the hollow fiber bioreactor (HFB) used for the cell culture was monitored with the use of proton magnetic resonance imaging ((1)H MRI). In addition, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was used in combination with HPLC (high performance liquid chromatography) to evaluate structural changes in the proteins contained in treated cells. The study showed that incorporation of antibodies into targeted lipoplex results in more efficient delivery of the complex to tumor cells. The viability of cells decreased mostly due to cellular uptake of lipoplex and binding of the antibodies to the cellular surface receptor. The data also demonstrate that HA could be used to enhance treatment efficacy of trastuzumab and anti-HER-2 (clone CB11) in breast cancer cell cultures.
Bartusik
Dorota
D
National Research Council Canada, Institute for Biodiagnostics (West), Calgary, Alberta, Canada. Dorota.Bartusik@gmail.com
Tomanek
Boguslaw
B
Lattová
Erika
E
Perreault
Hélène
H
Fallone
Gino
G
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000276:immunology / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004247:DNA / Q000008:administration & dosage; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D006820:Hyaluronic Acid / Q000008:administration & dosage; D008055:Lipids / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging / Q000379:methods; D010957:Plasmids / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004247:DNA; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D008055:Lipids; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C086724:Lipofectamine