GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer

BMC Cancer

Research Article

Diego H Castrillon¹  Christina L Roland²  Kristi D Lynn³  Rolf A Brekken⁴  D Gomika Udugamasooriya⁵  Thomas J Kodadek⁶ 

[1] Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., 76259, Dallas, TX, USA;Division of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, 5323 Harry Hines Blvd., 76259, Dallas, TX, USA;Division of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, 5323 Harry Hines Blvd., 76259, Dallas, TX, USA;Division of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, 5323 Harry Hines Blvd., 76259, Dallas, TX, USA;Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, 6000 Harry Hines Blvd., 76259, Dallas, TX, USA;Division of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, 5323 Harry Hines Blvd., 76259, Dallas, TX, USA;Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, 6000 Harry Hines Blvd., 76259, Dallas, TX, USA;Department of Pharmacology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., 75390, Dallas, TX, USA;Division of Translational Research, Department of Internal Medicine, UT Southwestern Medical Center, 6000 Harry Hines Blvd., 76259, Dallas, TX, USA;Advanced Imaging Research Center, UT Southwestern Medical Center, 6000 Harry Hines Blvd., 76259, Dallas, TX, USA;Division of Translational Research, Department of Internal Medicine, UT Southwestern Medical Center, 6000 Harry Hines Blvd., 76259, Dallas, TX, USA;Department of Chemistry, The Scripps Research Institute, 130 Scripps Way, 33458, Jupiter, FL, USA;

关键词: Vascular Endothelial Growth Factor;    Doxorubicin;    Vascular Endothelial Growth Factor Expression;    Vascular Endothelial Growth Factor Level;    Macrophage Infiltration;   

DOI  :  10.1186/1471-2407-10-397

 received in 2010-03-25, accepted in 2010-07-30,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundVascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis under physiological and pathological conditions. Anti-VEGF therapy is a clinically proven strategy for the treatment of a variety of cancers including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the dominant angiogenic signaling receptor, it has become an important target in the development of novel anti-angiogenic therapies. We have reported previously the development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising anti-angiogenic activity in vitro and in vivo.MethodsIn the current study, we utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested alone or in combination with doxorubicin for in vivo efficacy in the MMTV-PyMT transgenic model of breast cancer.ResultsThe derivative GU81 has increased in vitro efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81 alone) had no effect on tumor weight, histology, tumor fat content, or tumor growth index. However, GU81 is able to significantly to reduce total vascular area as a single agent. GU81 used in combination with doxorubicin significantly reduced tumor weight and growth index compared to all other treatment groups. Furthermore, treatment with combination therapy significantly arrested tumor progression at the premalignant stage, resulting in increased tumor fat content. Interestingly, treatment with GU81 alone increased tumor-VEGF levels and macrophage infiltration, an effect that was abrogated when used in combination with doxorubicin.ConclusionThis study demonstrates the VEGFR2 antagonist peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous murine MMTV-PyMT breast tumors.

【 授权许可】

Unknown   
© Lynn et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.