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Growth inhibition of experimental non‐Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN‐238
Author(s) -
Keller Gunhild,
Engel Jörg B.,
Schally Andrew V.,
Nagy Attila,
Hammann Brian,
Halmos Gabor
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20806
Subject(s) - somatostatin , somatostatin receptor , receptor , somatostatin receptor 2 , medicine , cytotoxic t cell , endocrinology , somatostatin receptor 1 , radioligand , in vivo , chemistry , biology , pharmacology , in vitro , biochemistry , microbiology and biotechnology
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. © 2004 Wiley‐Liss, Inc.