The inhibitory effect of a novel cytotoxic somatostatin analogue AN-162 on experimental glioblastoma.

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.

• Authors: E Pozsgai, A V Schally, G Halmos, F Rick, S Bellyei
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 42 Issue 11 Pg. 781-6 (Oct 2010) ISSN: 1439-4286 [Electronic] Germany
• PMID: 20665426 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Aniline Compounds
• RNA, Messenger
• Receptors, Somatostatin
• N-(2-diethylaminoethyl)-N-(2-hydroxy-2-phenylethyl)-2,5-dichloroaniline
• Somatostatin
• 2-Hydroxyphenethylamine
• Doxorubicin

Topics

• 2-Hydroxyphenethylamine (analogs & derivatives, pharmacology, therapeutic use)
• Aniline Compounds (pharmacology, therapeutic use)
• Animals
• Biological Assay
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Doxorubicin (pharmacology)
• Drug Screening Assays, Antitumor
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioblastoma (chemically induced, drug therapy, genetics, pathology)
• Mice
• RNA, Messenger (genetics, metabolism)
• Receptors, Somatostatin (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Somatostatin (analogs & derivatives)