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

Int J Cancer. 1999 Aug 12;82(4):592-8. doi: 10.1002/(sici)1097-0215(19990812)82:4<592::aid-ijc20>;2-0.


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-NH(2)) 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 sst(2) and sst(5) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use*
  • Breast Neoplasms / blood
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Division
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Doxorubicin / therapeutic use
  • Female
  • Growth Hormone / blood
  • Humans
  • Immunotoxins / administration & dosage
  • Immunotoxins / therapeutic use*
  • Luteinizing Hormone / blood
  • Mice
  • Mice, Nude
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use
  • Receptors, Somatostatin / blood
  • Transplantation, Heterologous


  • AN 238
  • Antibiotics, Antineoplastic
  • Immunotoxins
  • Pyrroles
  • Receptors, Somatostatin
  • AN 204
  • Doxorubicin
  • Luteinizing Hormone
  • Growth Hormone