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

Anjuli Datta, Richard P. Kitson, Yaming Xue, Gheath Al-Atrash, Andrew P. Mazar, Terence R. Jones, Ronald H. Goldfarb

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)451-457
Number of pages7
JournalIn Vivo
Volume16
Issue number6
StatePublished - 2002

Keywords

  • Chemo/anti-angiogenic therapy
  • Metastasis
  • uPA/uPAR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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