Growth inhibition of experimental non-Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN-238

Gunhild Keller, Jörg B. Engel, Andrew V. Schally, Attila Nagy, Brian Hammann, Gabor Halmos

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The cytotoxic analogue of somatostatin, AN-238, consisting of 2-pyrrolinodoxorubicin (AN-201), a superactive derivative of doxorubicin (DOX), linked to somatostatin analogue carrier RC-121 binds with high affinity to receptors for somatostatin and can be targeted to tumors that express these receptors. Because somatostatin receptors are found in a high percentage of human non-Hodgkin's lymphomas (NHLs), we evaluated the antitumor effect of AN-238 in 2 human NHL cell lines in vivo. Nude mice bearing xenografts of RL and HT human NHL were treated with AN-238 or its components at equimolar doses, and antitumor effects were determined. Expression of mRNA for somatostatin receptor subtypes was measured by RT-PCR, and the presence of somatostatin receptors was determined by radioligand binding. Toxicity was evaluated by following white blood cell count (WBC) and body weight. AN-238 significantly (p < 0.05) inhibited growth of RL and HT xenografts and prolonged the tumor doubling time. Cytotoxic radical AN-201, the unconjugated mixture of somatostatin analogue RC-121 and AN-201 or RC-121 alone had no significant effects. Blockade of somatostatin receptors by excess RC-121 abolished the effect of AN-238, demonstrating targeting. Expression of somatostatin receptors was not changed after repeated treatment with AN-238. AN-201, but not AN-238, significantly lowered the WBC and caused a greater decrease in body weight than AN-238. Our findings demonstrate that targeted chemotherapy with AN-238 can strongly inhibit the growth of NHL cells, which express somatostatin receptors. AN-238 could be considered for the treatment for patients with NHL.

Original languageEnglish (US)
Pages (from-to)831-835
Number of pages5
JournalInternational Journal of Cancer
Volume114
Issue number5
DOIs
StatePublished - May 1 2005
Externally publishedYes

Keywords

  • AN-238
  • Non-Hodgkin's lymphoma
  • Somatostatin receptor
  • Targeted chemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Growth inhibition of experimental non-Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN-238'. Together they form a unique fingerprint.

  • Cite this