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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.

Publication ,  Journal Article
Kahán, Z; Nagy, A; Schally, AV; Hebert, F; Sun, B; Groot, K; Halmos, G
Published in: Int J Cancer
August 12, 1999

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.

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Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

August 12, 1999

Volume

82

Issue

4

Start / End Page

592 / 598

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Receptors, Somatostatin
  • Pyrroles
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Luteinizing Hormone
  • Immunotoxins
  • Humans
  • Growth Hormone
 

Citation

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Kahán, Z., Nagy, A., Schally, A. V., Hebert, F., Sun, B., Groot, K., & Halmos, G. (1999). 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, 82(4), 592–598. https://doi.org/10.1002/(sici)1097-0215(19990812)82:4<592::aid-ijc20>3.0.co;2-0
Kahán, Z., A. Nagy, A. V. Schally, F. Hebert, B. Sun, K. Groot, and G. Halmos. “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 82, no. 4 (August 12, 1999): 592–98. https://doi.org/10.1002/(sici)1097-0215(19990812)82:4<592::aid-ijc20>3.0.co;2-0.
Kahán, Z., et al. “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, vol. 82, no. 4, Aug. 1999, pp. 592–98. Pubmed, doi:10.1002/(sici)1097-0215(19990812)82:4<592::aid-ijc20>3.0.co;2-0.
Kahán Z, Nagy A, Schally AV, Hebert F, Sun B, Groot K, Halmos G. 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):592–598.
Journal cover image

Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

August 12, 1999

Volume

82

Issue

4

Start / End Page

592 / 598

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Receptors, Somatostatin
  • Pyrroles
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Luteinizing Hormone
  • Immunotoxins
  • Humans
  • Growth Hormone