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Targeted cytotoxic analogue of bombesin/gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice.

Publication ,  Journal Article
Kiaris, H; Schally, AV; Nagy, A; Sun, B; Armatis, P; Szepeshazi, K
Published in: Br J Cancer
November 1999

Recently, we developed a powerful cytotoxic analogue of bombesin AN-215, in which the bombesin-like carrier peptide Gln-Trp-Ala-Val-Gly-His-Leu-psi(CH2-NH)-Leu-NH2 (RC-3094) is conjugated to a potent derivative of doxorubicin, 2-pyrrolinodoxorubicin (AN-201). Small-cell lung carcinomas (SCLCs) are known to express high levels of bombesin receptors. We evaluated whether these receptors could be used for targeting cytotoxic bombesin analogue to H-69 SCLC cells. H-69 cells were xenografted into male nude mice, which then received an intravenous injection of AN-215, cytotoxic radical AN-201, the carrier peptide RC-3094 alone or unconjugated mixture of RC-3094 and AN-201. The levels of mRNA for bombesin receptor subtypes were evaluated by reverse transcription-polymerase chain reaction. In vitro, both the analogue AN-215 and the radical AN-201 showed strong antiproliferative effects on H-69 cells, AN-215 requiring more time to exert its action at 10(-8) M concentration than AN-201. In vivo, the growth of H-69 SCLC tumours was significantly inhibited by the treatment with 200 nmol kg(-1) of AN-215, while equimolar doses of the cytotoxic radical AN-201 or the mixture of AN-201 and the carrier peptide were toxic and produced only a minor tumour inhibition as compared with control groups. mRNA for bombesin receptor subtypes 2 (BRS-2) and 3 (BRS-3) was detected in H-69 tumours. The mRNA levels for BRS-3, but not for BRS-2, were lower in the AN-215-treated tumours as compared with controls. Our results demonstrate that the cytotoxic bombesin analogue AN-215 could be considered for targeted therapy of tumours, such as SCLC, that express bombesin receptors.

Duke Scholars

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Published In

Br J Cancer

DOI

ISSN

0007-0920

Publication Date

November 1999

Volume

81

Issue

6

Start / End Page

966 / 971

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Bombesin
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Male
  • Lung Neoplasms
  • Humans
 

Citation

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Kiaris, H., Schally, A. V., Nagy, A., Sun, B., Armatis, P., & Szepeshazi, K. (1999). Targeted cytotoxic analogue of bombesin/gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice. Br J Cancer, 81(6), 966–971. https://doi.org/10.1038/sj.bjc.6690794
Kiaris, H., A. V. Schally, A. Nagy, B. Sun, P. Armatis, and K. Szepeshazi. “Targeted cytotoxic analogue of bombesin/gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice.Br J Cancer 81, no. 6 (November 1999): 966–71. https://doi.org/10.1038/sj.bjc.6690794.
Kiaris H, Schally AV, Nagy A, Sun B, Armatis P, Szepeshazi K. Targeted cytotoxic analogue of bombesin/gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice. Br J Cancer. 1999 Nov;81(6):966–71.
Kiaris, H., et al. “Targeted cytotoxic analogue of bombesin/gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice.Br J Cancer, vol. 81, no. 6, Nov. 1999, pp. 966–71. Pubmed, doi:10.1038/sj.bjc.6690794.
Kiaris H, Schally AV, Nagy A, Sun B, Armatis P, Szepeshazi K. Targeted cytotoxic analogue of bombesin/gastrin-releasing peptide inhibits the growth of H-69 human small-cell lung carcinoma in nude mice. Br J Cancer. 1999 Nov;81(6):966–971.

Published In

Br J Cancer

DOI

ISSN

0007-0920

Publication Date

November 1999

Volume

81

Issue

6

Start / End Page

966 / 971

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Bombesin
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Male
  • Lung Neoplasms
  • Humans