The inhibitory effect of a novel cytotoxic somatostatin analogue AN-162 on experimental glioblastoma.
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.
Pozsgai
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Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, Miami, FL 33125, USA.
Schally
A V
AV
Halmos
G
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Rick
F
F
Bellyei
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D015078:2-Hydroxyphenethylamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000814:Aniline Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001681:Biological Assay; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives*
D000814:Aniline Compounds; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C000956:N-(2-diethylaminoethyl)-N-(2-hydroxy-2-phenylethyl)-2,5-dichloroaniline; D013004:Somatostatin; D015078:2-Hydroxyphenethylamine; D004317:Doxorubicin