TY - JOUR
T1 - Inhibition of growth of MX-1, MCF-7-MIII and MDA-MB-231 human breast cancer xenografts after administration of a targeted cytotoxic analog of somatostatin, AN-238
AU - Kahán, Zsuzsanna
AU - Nagy, Attila
AU - Schally, Andrew V.
AU - Hebert, Francine
AU - Sun, Baodong
AU - Groot, Kate
AU - Halmos, Gábor
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - Since somatostatin (sst) receptors are expressed in a high percentage of human breast cancers, we studied the effects of a targeted cytotoxic somatostatin analog (AN-238) formed by linking the highly active doxorubicin (DOX) derivative 2-pyrrolino-DOX (AN-201) to octapeptide RC-121 (D-Phe-Cys- Tyr-D-Trp-Lys-Val-Cys-Thr-NH2) in 3 human breast cancer models. The models included estrogen-independent MDA-MB-231 and MX-1 and estrogen-sensitive MCF- 7-MIII tumors. Nude mice bearing xenografts of these cancers were injected i.v. with 250 nmol/kg doses of cytotoxic radical AN-201, cytotoxic analog AN- 238 or the unconjugated mixture of AN-201 and sst analog RC-121. Significant inhibition of growth of MDA-MB-231, MX-1 and MCF-7-MIII tumors was observed 1 week after injection of a single dose of cytotoxic analog AN-238. The volume of MDA-MB-231 tumors remained significantly decreased 3 weeks after treatment. The volumes and weights of MCF-7-MIII tumors continued to be significantly reduced 60 days after therapy with AN-238. AN-238 also caused complete regression of MX-1 tumors in 5 of 10 animals, which remained tumor- free 60 days after treatment. In contrast, after treatment with cytotoxic radical AN-201, MDA-MB-231 and MCF-7-MIII tumors grew steadily and the regression of MX-1 tumors was only transitory in most animals. Toxicity of AN-201 was much greater than that of AN-238, as measured by animal deaths, loss of body weight and leukopenia. High-affinity sst receptors and mRNA for both sst2 and sst5 subtypes were found in all 3 tumor lines. Expression of sst receptors was not significantly affected by treatment with AN-238. Our results indicate that the cytotoxic somatostatin analog AN-238 efficaciously inhibits growth of human breast cancers expressing sst receptor subtypes 2 and 5.
AB - Since somatostatin (sst) receptors are expressed in a high percentage of human breast cancers, we studied the effects of a targeted cytotoxic somatostatin analog (AN-238) formed by linking the highly active doxorubicin (DOX) derivative 2-pyrrolino-DOX (AN-201) to octapeptide RC-121 (D-Phe-Cys- Tyr-D-Trp-Lys-Val-Cys-Thr-NH2) in 3 human breast cancer models. The models included estrogen-independent MDA-MB-231 and MX-1 and estrogen-sensitive MCF- 7-MIII tumors. Nude mice bearing xenografts of these cancers were injected i.v. with 250 nmol/kg doses of cytotoxic radical AN-201, cytotoxic analog AN- 238 or the unconjugated mixture of AN-201 and sst analog RC-121. Significant inhibition of growth of MDA-MB-231, MX-1 and MCF-7-MIII tumors was observed 1 week after injection of a single dose of cytotoxic analog AN-238. The volume of MDA-MB-231 tumors remained significantly decreased 3 weeks after treatment. The volumes and weights of MCF-7-MIII tumors continued to be significantly reduced 60 days after therapy with AN-238. AN-238 also caused complete regression of MX-1 tumors in 5 of 10 animals, which remained tumor- free 60 days after treatment. In contrast, after treatment with cytotoxic radical AN-201, MDA-MB-231 and MCF-7-MIII tumors grew steadily and the regression of MX-1 tumors was only transitory in most animals. Toxicity of AN-201 was much greater than that of AN-238, as measured by animal deaths, loss of body weight and leukopenia. High-affinity sst receptors and mRNA for both sst2 and sst5 subtypes were found in all 3 tumor lines. Expression of sst receptors was not significantly affected by treatment with AN-238. Our results indicate that the cytotoxic somatostatin analog AN-238 efficaciously inhibits growth of human breast cancers expressing sst receptor subtypes 2 and 5.
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U2 - 10.1002/(SICI)1097-0215(19990812)82:4<592::AID-IJC20>3.0.CO;2-0
DO - 10.1002/(SICI)1097-0215(19990812)82:4<592::AID-IJC20>3.0.CO;2-0
M3 - Article
C2 - 10404076
AN - SCOPUS:0032816763
VL - 82
SP - 592
EP - 598
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -