Inhibition of breast cancer metastasis by dual liposomes to disturb complex formation.
The interaction between tumour cells and blood components, mainly platelets, plays an important role in metastasis. In this study, the anti-metastatic effect of vesicles containing the cytotoxic drug perifosine (OPP) and the haemostatic inhibitor dipyridamole (DIP) was tested. These dual liposomes (DIP/OPP-L) encapsulating up to 400microg DIP/ml and 6mM OPP were prepared by extrusion technique. In vitro, DIP/OPP-L significantly inhibited the aggregation of platelets and reduced their adhesion to immobilized MT3 cells by up to 60% and 24.7%, respectively. Complex formation between platelets and tumour cells in vitro was completely prevented by DIP/OPP-vesicles. These combinatory liposomes also inhibited the metastatic capacity of circulating tumour cells by reducing the complex formation with platelets. Formation of lung and extrapulmonary metastases after intravenous administration of MT3 breast cancer cells was significantly reduced when mice were treated with a single intravenous dose of DIP/OPP-L containing 100nmol lipid 6h before tumour cell inoculation.
Wenzel
Jane
J
Charite, Campus Benjamin Franklin, Medical Clinic IV, Nephrology, Berlin, Germany.
Zeisig
Reiner
R
Fichtner
Iduna
I
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004176:Dipyridamole / Q000008:administration & dosage* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D000090023:Metallothionein 3; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating / Q000187:drug effects; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004338:Drug Combinations; D008081:Liposomes; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D010975:Platelet Aggregation Inhibitors; D010767:Phosphorylcholine; C105905:perifosine; D004176:Dipyridamole