Targeting of cytotoxic bombesin analog AN-215 to H-69 small cell lung carcinoma as demonstrated by semi-quantitative microsatellite analysis in vitro

H. Kiaris, A. V. Schally, A. Nagy, P. Armatis

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Targeting of cytotoxic peptide analogs represents a modern approach to cancer chemotherapy because it greatly reduces peripheral toxicity. Recently, we developed a powerful cytotoxic analog of bombesin, AN-215, consisting of the superactive derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201) linked to the bombesin-like carrier peptide Gln-Trp-Ala-Val-Gly-His-Leu- ψ(CH2-NH)-Leu-NH2. This cytotoxic analog of bombesin was designed to be targeted to tumors that express bombesin receptors, such as small cell lung carcinoma (SCLC). In the present study we investigated whether targeting of AN-215 to bombesin receptor-positive cell line, such as NCI-H-69 SCLC, in the presence of the bombesin receptor-negative non-SCLC cell line NCI-H-157, could be demonstrated in vitro by semi-quantitative polymerase chain reaction (PCR) amplification of microsatellite markers. NCI-H-69 cells were co- cultured in vitro with NCI-H-157 non-SCLC cells and exposed to 5 nM AN-215 or AN-201 for 4 h. Untreated cells were used as controls. The cells were then cultured for 4 days in the absence of cytotoxic agents and genomic DNA was extracted for microsatellite analysis with the marker D8S264 for which specific alleles for each cell line could be identified. Semi-quantitative analysis of the intensity of the alleles that correspond to each cell line indicated that AN-201 has no selectivity for any of the cell lines, while AN- 215 was targeted specifically to H-69 cells. Thus, cytotoxic bombesin analog AN-215 can be targeted to tumors that express bombesin receptors, such as SCLC. Assays based on the co-culture of heterogeneous cell populations followed by microsatellite analysis may be useful for initial screening of targeted cytotoxic analogs.

Original languageEnglish (US)
Pages (from-to)266-270
Number of pages5
JournalTumor Targeting
Volume4
Issue number4
StatePublished - Dec 1 1999
Externally publishedYes

Keywords

  • Cancer therapy
  • Genetic heterogeneity
  • H-157
  • Microsatellite markers
  • SCLC
  • Semi-quantitative PCR
  • Targeted cytotoxic analogs

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

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