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In vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215.

Publication ,  Journal Article
Plonowski, A; Nagy, A; Schally, AV; Sun, B; Groot, K; Halmos, G
Published in: Int J Cancer
November 15, 2000

The effectiveness of chemotherapy targeted to bombesin (BN) receptors was evaluated in nude mice bearing PC-3 human androgen-independent prostate cancers. Cytotoxic BN analogue AN-215, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to BN-like carrier peptide RC-3094, was injected i.v. at 150 nmol/kg on days 1, 11 and 21. After treatment with AN-215, tumor volume was 69% (p < 0.01) smaller than that in controls and tumor doubling time was extended from 8.5 +/- 0.7 days to 20.3 +/- 3.5 days (p < 0.05). Cytotoxic radical AN-201, carrier RC-3094 and their unconjugated mixture administered at the same dosage were ineffective. The mortality rate was 12.5% in the AN-201 group and 16.7% in the group treated with the mixture, but no deaths occurred in mice receiving AN-215. Because the ester bond linking AN-201 to the carrier molecule is hydrolyzed much faster in mouse serum than in human serum, in the second experiment we investigated the tolerance to AN-215 and its effect in nude mice bearing PC-3 tumors after pharmacological inhibition of serum carboxylesterases. Two applications of AN-201 at 200 nmol/kg were lethal, whereas no mortality was observed after 4 injections of AN-215 at the same dose. Administration of 200 nmol/kg AN-215 on days 1, 7, 17 and 26 again produced 69% tumor inhibition. BN receptors on membranes of PC-3 tumors were detected by (125)I-[Tyr(4)]BN binding, and expression of mRNA for BRS-3 and GRP-R subtypes was also found. AN-215 showed a high affinity to PC-3 tumors, displacing the radioligand at an IC(50) of 12.95 +/- 0.35 nM. Because BN receptors are present on primary and metastatic prostate cancer, targeted chemotherapy with AN-215 might benefit patients with advanced prostatic carcinoma who relapsed androgen ablation.

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Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

November 15, 2000

Volume

88

Issue

4

Start / End Page

652 / 657

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Receptors, Bombesin
  • Pyrroles
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Male
  • Humans
 

Citation

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Chicago
ICMJE
MLA
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Plonowski, A., Nagy, A., Schally, A. V., Sun, B., Groot, K., & Halmos, G. (2000). In vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215. Int J Cancer, 88(4), 652–657. https://doi.org/10.1002/1097-0215(20001115)88:4<652::aid-ijc21>3.0.co;2-1
Plonowski, A., A. Nagy, A. V. Schally, B. Sun, K. Groot, and G. Halmos. “In vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215.Int J Cancer 88, no. 4 (November 15, 2000): 652–57. https://doi.org/10.1002/1097-0215(20001115)88:4<652::aid-ijc21>3.0.co;2-1.
Plonowski A, Nagy A, Schally AV, Sun B, Groot K, Halmos G. In vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215. Int J Cancer. 2000 Nov 15;88(4):652–7.
Plonowski, A., et al. “In vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215.Int J Cancer, vol. 88, no. 4, Nov. 2000, pp. 652–57. Pubmed, doi:10.1002/1097-0215(20001115)88:4<652::aid-ijc21>3.0.co;2-1.
Plonowski A, Nagy A, Schally AV, Sun B, Groot K, Halmos G. In vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215. Int J Cancer. 2000 Nov 15;88(4):652–657.
Journal cover image

Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

November 15, 2000

Volume

88

Issue

4

Start / End Page

652 / 657

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Receptors, Bombesin
  • Pyrroles
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Mice, Nude
  • Mice
  • Male
  • Humans