Abstract
Glioblastoma multiforme is the most common and most aggressive type of high grade tumor with a poor prognosis upon discovery. Based on earlier promising results earned with AN-162, a doxorubicin molecule linked to somatostatin (SST) analogue RC-160, it was our aim to determine the effect of AN-162 on DBTRG-05 glioblastoma cell line, and to test its efficacy in experimental brain tumors. We detected the expression of mRNA for somatostatin receptor (SSTR) subtypes 2 and 3 in DBTRG-05 cells with RT-PCR. Using ligand competition assay, specific high affinity receptors for somatostatin were found. The MTT assay showed that both AN-162 and doxorubicin (DOX) significantly inhibited cell proliferation and that there was no significant difference between the effects in vitro. Nude mice were xenografted with DBTRG-05 glioblastoma tumors. AN-162 showed a significant inhibition of tumor growth compared with the control group and the groups treated with equimolar doses of doxorubicin, somatostatin analogue RC-160, or the unconjugated mixture of doxorubicin plus RC-160. The tumor doubling time in the group of animals treated with AN-162 was extended and was significantly different from doubling times in the control group and in the other treatment groups. Our study clearly demonstrates a potent inhibitory effect of AN-162 in experimental glioblastoma, thus suggesting the possibility of its utilization in patients suffering from malignant brain cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 781-786 |
| Number of pages | 6 |
| Journal | Hormone and Metabolic Research |
| Volume | 42 |
| Issue number | 11 |
| DOIs | |
| State | Published - Oct 11 2010 |
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Keywords
- AN-162
- doxorubicine
- glioblastoma
- somatostatin
- targeted therapy
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Clinical Biochemistry
- Biochemistry, medical
- Endocrinology, Diabetes and Metabolism
Cite this
The inhibitory effect of a novel cytotoxic somatostatin analogue AN-162 on experimental glioblastoma. / Pozsgai, E.; Schally, Andrew V; Halmos, G.; Rick, F.; Bellyei, S.
In: Hormone and Metabolic Research, Vol. 42, No. 11, 11.10.2010, p. 781-786.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The inhibitory effect of a novel cytotoxic somatostatin analogue AN-162 on experimental glioblastoma
AU - Pozsgai, E.
AU - Schally, Andrew V
AU - Halmos, G.
AU - Rick, F.
AU - Bellyei, S.
PY - 2010/10/11
Y1 - 2010/10/11
N2 - Glioblastoma multiforme is the most common and most aggressive type of high grade tumor with a poor prognosis upon discovery. Based on earlier promising results earned with AN-162, a doxorubicin molecule linked to somatostatin (SST) analogue RC-160, it was our aim to determine the effect of AN-162 on DBTRG-05 glioblastoma cell line, and to test its efficacy in experimental brain tumors. We detected the expression of mRNA for somatostatin receptor (SSTR) subtypes 2 and 3 in DBTRG-05 cells with RT-PCR. Using ligand competition assay, specific high affinity receptors for somatostatin were found. The MTT assay showed that both AN-162 and doxorubicin (DOX) significantly inhibited cell proliferation and that there was no significant difference between the effects in vitro. Nude mice were xenografted with DBTRG-05 glioblastoma tumors. AN-162 showed a significant inhibition of tumor growth compared with the control group and the groups treated with equimolar doses of doxorubicin, somatostatin analogue RC-160, or the unconjugated mixture of doxorubicin plus RC-160. The tumor doubling time in the group of animals treated with AN-162 was extended and was significantly different from doubling times in the control group and in the other treatment groups. Our study clearly demonstrates a potent inhibitory effect of AN-162 in experimental glioblastoma, thus suggesting the possibility of its utilization in patients suffering from malignant brain cancer.
AB - Glioblastoma multiforme is the most common and most aggressive type of high grade tumor with a poor prognosis upon discovery. Based on earlier promising results earned with AN-162, a doxorubicin molecule linked to somatostatin (SST) analogue RC-160, it was our aim to determine the effect of AN-162 on DBTRG-05 glioblastoma cell line, and to test its efficacy in experimental brain tumors. We detected the expression of mRNA for somatostatin receptor (SSTR) subtypes 2 and 3 in DBTRG-05 cells with RT-PCR. Using ligand competition assay, specific high affinity receptors for somatostatin were found. The MTT assay showed that both AN-162 and doxorubicin (DOX) significantly inhibited cell proliferation and that there was no significant difference between the effects in vitro. Nude mice were xenografted with DBTRG-05 glioblastoma tumors. AN-162 showed a significant inhibition of tumor growth compared with the control group and the groups treated with equimolar doses of doxorubicin, somatostatin analogue RC-160, or the unconjugated mixture of doxorubicin plus RC-160. The tumor doubling time in the group of animals treated with AN-162 was extended and was significantly different from doubling times in the control group and in the other treatment groups. Our study clearly demonstrates a potent inhibitory effect of AN-162 in experimental glioblastoma, thus suggesting the possibility of its utilization in patients suffering from malignant brain cancer.
KW - AN-162
KW - doxorubicine
KW - glioblastoma
KW - somatostatin
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=77957575775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77957575775&partnerID=8YFLogxK
U2 - 10.1055/s-0030-1261955
DO - 10.1055/s-0030-1261955
M3 - Article
C2 - 20665426
AN - SCOPUS:77957575775
VL - 42
SP - 781
EP - 786
JO - Hormone and Metabolic Research
JF - Hormone and Metabolic Research
SN - 0018-5043
IS - 11
ER -