Combined chemo/anti-angiogenic cancer therapy against Lewis lung carcinoma (3LL) pulmonary metastases

Å6 is an eight amino acid peptide derived from the non-receptor binding region of urokinase plasminogen activator (uPA), which interferes with the uPA/uPA receptor system. Å6 has been synthesized as a potential anti-angiogenic, anti-cancer agent. The current study has investigated the potential therapeutic activity of Å6 in the Lewis lung carcinoma (3LL) model of pulmonary metastasis Å6 was found to have direct anti-tumor activity against establish 3LL pulmonary metastases at a low tumor burden (10-20 colonies per lung) and was therapeutic in combination with cyclophosphamide at high tumor burdens (>100 colonies per lung). Mechanistic studies have revealed that Å6 directly inhibits the invasion of 3LL cells through a Matrigel model basement membrane by 40-45%. Moreover, treatment with either Å6 or doxorubicin resulted in thicker tubes in endothelial tube formation studies. Our results suggest that Å6, by virtue of its anti-invasive and anti-angiogenic properties, might work additvely or synergistically with chemotherapeutic agents and thereby contribute to enhanced therapy of establish 3LL cancer metastases.