Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215

Z. Szereday, Andrew V Schally, A. Nagy, A. Plonowski, A. M. Bajo, G. Halmos, K. Szepeshazi, K. Groot

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Some brain tumours, such as glioblastomas express high levels of receptors for bombesin/gastrin releasing peptide. We investigated whether bombesin/gastrin releasing peptide receptors found in glioblastoma cell lines can be utilised for targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin-like peptide carrier. This study reports the effect of AN-215 on the growth of U-87MG human glioblastomas xenografted into nude mice. High affinity binding of AN-215 to U-87MG tumours was characterised by an IC50 value of 4.0 ± 0.1 nM, as determined by radioreceptor assays. mRNA analyses revealed the presence of mRNA for BN receptor subtypes 1 and 2. Treatment with AN-215 significantly (P < 0.05) extended tumour doubling time from 4.54 ± 0.2 days to 8.18 ± 1.8 days and inhibited tumour growth as demonstrated by a 69.6% reduction in final tumour volume (P < 0.001) and a 64.6% decrease in tumour weight as compared to controls. Cytotoxic radical AN-201 at the same dose was ineffective. The antitumour effect of AN-215 could be blocked by pretreatment with an excess of a bombesin antagonist, indicating that the action of this cytotoxic analogue is receptor-mediated. Our results suggest that patients with inoperable brain tumours such as malignant gliomas may benefit from targeted chemotherapy based on cytotoxic bombesin analogue AN-215.

Original languageEnglish
Pages (from-to)1322-1327
Number of pages6
JournalBritish Journal of Cancer
Volume86
Issue number8
DOIs
StatePublished - Apr 22 2002
Externally publishedYes

Fingerprint

Bombesin
Glioblastoma
Nude Mice
Bombesin Receptors
Tumor Burden
Brain Neoplasms
Doxorubicin
Therapeutics
Neoplasms
Radioligand Assay
Messenger RNA
Growth
Glioma
Inhibitory Concentration 50
AN 215
Drug Therapy
Cell Line
Peptides

Keywords

  • Bombesin receptor
  • Doxorubicin
  • RT-PCR
  • Tumour targeting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215. / Szereday, Z.; Schally, Andrew V; Nagy, A.; Plonowski, A.; Bajo, A. M.; Halmos, G.; Szepeshazi, K.; Groot, K.

In: British Journal of Cancer, Vol. 86, No. 8, 22.04.2002, p. 1322-1327.

Research output: Contribution to journalArticle

Szereday, Z. ; Schally, Andrew V ; Nagy, A. ; Plonowski, A. ; Bajo, A. M. ; Halmos, G. ; Szepeshazi, K. ; Groot, K. / Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215. In: British Journal of Cancer. 2002 ; Vol. 86, No. 8. pp. 1322-1327.
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