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 language | English |
|---|---|
| Pages (from-to) | 1322-1327 |
| Number of pages | 6 |
| Journal | British Journal of Cancer |
| Volume | 86 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 22 2002 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215
AU - Szereday, Z.
AU - Schally, Andrew V
AU - Nagy, A.
AU - Plonowski, A.
AU - Bajo, A. M.
AU - Halmos, G.
AU - Szepeshazi, K.
AU - Groot, K.
PY - 2002/4/22
Y1 - 2002/4/22
N2 - 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.
AB - 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.
KW - Bombesin receptor
KW - Doxorubicin
KW - RT-PCR
KW - Tumour targeting
UR - http://www.scopus.com/inward/record.url?scp=0037156945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037156945&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6600235
DO - 10.1038/sj.bjc.6600235
M3 - Article
C2 - 11953892
AN - SCOPUS:0037156945
VL - 86
SP - 1322
EP - 1327
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 8
ER -