1. ¹Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan
2. ²Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
3. ³Division of Cancer-related Genes, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan
4. ⁴Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, Yamagata, Japan
5. ⁵Department of Oral Pathobiological Science, Hokkaido University Graduate Dental School, Hokkaido, Japan
6. ⁶Oncorex Inc., Sapparo, Hokkaido, Japan

Correspondence: Dr M Kobayashi, Oncorex Inc., Kita-21, Nishi-12, Kita-Ku, Sapporo, Hokkaido 001-0021, Japan. E-mail: mkobaya@igm.hokudai.ac.jp

⁷Current address: Department of Biomolecular Function, Yamagata Graduate School of Medical Science, Yamagata, Japan.

Received 18 November 2005; Revised 28 February 2006; Accepted 22 April 2006; Published online 14 July 2006.

Abstract

We have recently reported that the intra-tumoral injection of adrenomedullin (AM) antagonist (AMA; AM (22|[ndash]|52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in severely combined immunodeficient (SCID) mice. In the present study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding AMA on the in vivo growth of cancer cell lines. We demonstrate that these treatments induce the regression of a pancreatic cancer cell line and a breast cancer cell line inoculated in SCID mice. Furthermore, CD31-positive cells disappear completely from tumor tissues, following treatment, indicating that neo-vascularization is entirely inhibited. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising alternative modality for treating human cancers.