Effects of camptothecin on tumor cell proliferation and angiogenesis when coupled to a bombesin analog used as a targeted delivery vector.

The camptothecin-bombesin conjugate termed DC-51-43, as a novel targeted drug delivery system, was examined in over 10 human tumor cell lines and shows a potent antiproliferative activity. This conjugate has also demonstrated its antitumor activity in our previous experiments. In our present study, we evaluate this conjugate for its antiangiogenic activity by in-vitro and in-vivo experiments. The camptothecin-bombesin conjugate and free camptothecin show potent in-vitro inhibitory activities of cell adhesion to various extracellular matrix components and integrins alphaVbeta3 and alphaVbeta5, not beta1/alphabeta1. This conjugate displays inhibitory activity to cell migration and invasion at concentrations of 10 micromol/l or above. This conjugate is also effective against in-vitro capillary-like tube formation of endothelial cells (at 40 micromol/l), and in-vivo angiogenesis as seen by blocking the spread of host mice endothelial cells into matrigel plugs. These experimental results support the fact that the camptothecin-bombesin conjugate has therapeutic activities against angiogenesis. By binding to bombesin receptor-expressing sites, this bombesin analog, consisting of 11 amino acids, is potentially a novel delivery vector for nonspecific cytotoxic agents.