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Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II.

Publication ,  Journal Article
Kahán, Z; Sun, B; Schally, AV; Arencibia, JM; Cai, RZ; Groot, K; Halmos, G
Published in: Cancer
March 15, 2000

BACKGROUND: The growth of breast carcinoma is promoted by autocrine growth factors such as the bombesin (BN)-like peptides and epidermal growth factor (EGF). The stimulatory action of BN-like peptides can be blocked by the use of BN/gastrin-releasing peptide (GRP) antagonists. METHODS: The authors investigated the effects of synthetic BN/GRP antagonists RC-3095 and RC-3940-II on tumor growth and the expression of mRNA for EGF receptors and three BN receptor subtypes in MDA-MB-468 human breast carcinoma. Athymic nude mice with xenografts of MDA-MB-468 human breast carcinoma were injected subcutaneously for 6 weeks with RC-3940-II at doses of 20 or 40 microg/day. In another study, the effects of RC-3940-II and RC-3095 were compared. RESULTS: RC-3940-II caused a significant and dose-dependent growth inhibition of MDA-MB-468 tumors in nude mice; therapy with either dose of RC-3940-II significantly (P<0.01) reduced the mean final tumor volume and weight compared with controls. RC-3940-II induced a persistent regression of > 50% of all tumors. One of 3 tumors treated with 20 microg of RC-3940-II and 3 of 5 tumors treated with 40 microg were found to have regressed completely by the end of the study. When RC-3940-II and RC-3095 were compared at the dose of 20 microg/day, both powerfully suppressed growth of MDA-MB-468 tumors, with RC-3940-II causing a complete regression of 2 tumors and RC-3095 a complete regression of 1 tumor. Receptor analyses of untreated MDA-MB-468 tumors revealed an overexpression of EGF receptors and two classes of binding sites for BN/GRP. mRNAs for receptors of GRP, neuromedin B, and BN receptor subtype-3 were detected by reverse transcriptase-polymerase chain reaction. CONCLUSIONS: A virtual arrest of growth or regression of MDA-MB-468 human breast carcinoma after therapy with RC-3940-II and RC-3095 indicates that these BN/GRP antagonists could provide a new treatment modality for breast tumors expressing BN and EGF receptors.

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Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

March 15, 2000

Volume

88

Issue

6

Start / End Page

1384 / 1392

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Remission Induction
  • Receptors, Bombesin
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Peptide Fragments
  • Oncology & Carcinogenesis
  • Neurokinin B
  • Neoplasm Transplantation
 

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Kahán, Z., Sun, B., Schally, A. V., Arencibia, J. M., Cai, R. Z., Groot, K., & Halmos, G. (2000). Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II. Cancer, 88(6), 1384–1392. https://doi.org/10.1002/(sici)1097-0142(20000315)88:6<1384::aid-cncr16>3.0.co;2-q
Kahán, Z., B. Sun, A. V. Schally, J. M. Arencibia, R. Z. Cai, K. Groot, and G. Halmos. “Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II.Cancer 88, no. 6 (March 15, 2000): 1384–92. https://doi.org/10.1002/(sici)1097-0142(20000315)88:6<1384::aid-cncr16>3.0.co;2-q.
Kahán Z, Sun B, Schally AV, Arencibia JM, Cai RZ, Groot K, et al. Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II. Cancer. 2000 Mar 15;88(6):1384–92.
Kahán, Z., et al. “Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II.Cancer, vol. 88, no. 6, Mar. 2000, pp. 1384–92. Pubmed, doi:10.1002/(sici)1097-0142(20000315)88:6<1384::aid-cncr16>3.0.co;2-q.
Kahán Z, Sun B, Schally AV, Arencibia JM, Cai RZ, Groot K, Halmos G. Inhibition of growth of MDA-MB-468 estrogen-independent human breast carcinoma by bombesin/gastrin-releasing peptide antagonists RC-3095 and RC-3940-II. Cancer. 2000 Mar 15;88(6):1384–1392.
Journal cover image

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

March 15, 2000

Volume

88

Issue

6

Start / End Page

1384 / 1392

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Remission Induction
  • Receptors, Bombesin
  • RNA, Messenger
  • Polymerase Chain Reaction
  • Peptide Fragments
  • Oncology & Carcinogenesis
  • Neurokinin B
  • Neoplasm Transplantation