Inhibition of breast cancer growth in vivo by antiangiogenesis gene therapy with adenovirus-mediated antisense-VEGF

S. A. Im, J. S. Kim, C. Gomez-Manzano, J. Fueyo, T. J. Liu, M. S. Cho, C. M. Seong, S. N. Lee, Y. K. Hong, W. K.A. Yung

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Increased expression of VEGF in several types of tumours has been shown to correlate with poor prognosis. We used a replication-deficient adenoviral vector containing antisense VEGF cDNA (Ad5CMV-αVEGF) to down-regulate VEGF expression and increase the efficiency of delivery of the antisense sequence in the human breast cancer cell line MDA231-MB. Transfection of these cells with Ad5CMV-αVEGF in vitro reduced secreted levels of VEGF protein without affecting cell growth. Moreover, injection of the Ad5CMV-αVEGF vector into intramammary xenografts of these cells established in nude mice inhibited tumour growth and reduced the amount of VEGF protein and the density of microvessels in those tumours relative to tumours treated with the control vector Ad5(dl312). Our results showed that antisense VEGF 165 cDNA was efficiently delivered in vivo via an adenoviral vector and that this treatment significantly inhibited the growth of established experimental breast tumours. The Ad5CMV-αVEGF vector may be useful in targeting the tumour vasculature in the treatment of breast cancer.

Original languageEnglish
Pages (from-to)1252-1257
Number of pages6
JournalBritish Journal of Cancer
Volume84
Issue number9
DOIs
StatePublished - 4 May 2001

Bibliographical note

Funding Information:
This study was supported in part by a grant from Ewha Womans University Medical College Graduates’ Alumnae Association Research Fund, Korea and by US National Institutes of Health grants CA-51148 and CA-55261. We thank Polly S Lee and Mary T Wang for helpful discussion and purification of the viruses, Louis Hau and Christine Wogan for editorial assistance.

Keywords

  • Adenovirus
  • Antiangiogenesis
  • Breast cancer
  • Gene therapy
  • VEGF

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