One of the preconditions of effective anticancer
therapy is efficient transfer of the therapeutic agent (chemotherapeutic) to
tumor cells. Fundamental barriers making
drug delivery and action difficult include underoxygenation, elevated interstitial pressure, poor and abnormal
tumor blood vascular network and acidic
tumor milieu. In this study we aimed at developing an optimized scheme of administering a combination of an angiogenesis-inhibiting
drug (
vasostatin) and a chemotherapeutic (
cyclophosphamide) in the therapeutic treatment of mice bearing experimental B16-F10
melanoma tumors. We report that the strongest
tumor growth inhibition was observed in mice that received two, three or four
vasostatin doses in combination with one injection of
cyclophosphamide (i.e., V2 + CTX, V3 + CTX or V4 + CTX schemes). Double administration of
vasostatin increases oxygenation of B16-F10
tumors. On the other hand, its five-fold administration lowers
tumor oxygenation, breaks down
tumor vascular network (increasing
hypoxia) and leads in consequence to death of
cancer cells and appearance of necrotic areas in the
tumor. A decreased
cyclophosphamide dose in combination with two doses of
vasostatin (V2 + CTX scheme) inhibits
tumor growth similarly to a larger dose of
cyclophosphamide alone.