Inhibition der Angiogenese durch kationische Liposomen: Ein neuer Zugang zur Unterdrückung des Tumorwachstums
Zusammenfassung
Therapy of tumors by inhibition of angiogenesis is a means of tumor treatment. This
possibility is a cell line unspecific influence. The angiogenesis in tumors starts through the influence of hypoxia. The consequence is
the excretion of the angiogenic factors VEGF, TNF-α , and EGF. A typical feature of
newly generated blood vessels is a strongly subordinate proliferation of endothelial
cells. This leads to a mosaic structure of blood vessels containing endothelial and tumor
cells. Proliferating endothelial cells in tumor vessels turned out to be the target for specific
uptake of cationic liposomes. To reach an inhibition of angiogenesis the cytostatic drug
paclitaxel was bound to cationic liposomes. The outcome of the research relating to the
proliferated endothelial cells in tumor vessels ends in the comparison of a conventional
cytostatic drug (TaxolTM) with paclitaxel bound to cationic liposomes. In this study a
tumor model was established with BALB/c mice. In this model stably with the lac-Z
gen transfected Renca- cells (renal carcinoma cells isolated from BALB/c mice) were
injected s.c. into the back flank of the mice. For induction of metastases in the lungs of
research animals the same cell line was injected into the tail vain. In all animal experiments one could see distinct effects in reduction of the growth of
tumors or the amount of metastases on the surface of the lungs from animals treated
with liposomal paclitaxel. Furthermore a reduction of tumors growth respectively reduction of the amount of
metastases could be seen in the treatment with cationic liposomes. This result of the test
is comparable with the conservative treatment of TaxolTM The histopathologic evaluation of this experiment shows a low amount of atrophy in the
liver cells in mice which were treated with liposomal paclitaxel. In the animal research carried out a higher efficiency on reduction of tumor growth and
metastasis of liposomal paclitaxel than with TaxolTM