Growth inhibition of human colon carcinoma cells by combinations of anti-epidermal growth factor-related growth factor antisense oligonucleotides

Nicola Normanno, Caterina Bianco, Vincenzo Damiano, Ernesto De Angelis, Mouna P. Selvam, Michele Grassi, Gabriella Magliulo, Giampaolo Tortora, Angelo R. Bianco, John Mendelsohn, David S. Salomon, Fortunato Ciardiello

Research output: Contribution to journalArticle

Abstract

GEO is a well-differentiated colon cancer cell line that coexpresses the epidermal growth factor-like growth factors CRIPTO (CR), amphiregulin (AR), and transforming growth factor or (TGF-α). Antisense 20-mer phosphorothioate oligodeoxynncleotides (AS S-oligos) directed against CR, AR, and TGF-α mRNAs were equipotent in their ability to inhibit both the anchorage dependent growth and the anchorage-independent growth (AIG) of GEO cells, with a 50% inhibitory concentration of about 5 μM in the AIG assay. A supraadditive effect was observed when a combination of S-oligos was used. For example, a combination of two different AS S-oligos (either AR + CR, or TGF-α + CR, or TGF-α + AR) at a concentration of 1 μM each (total concentration, 2 μM) resulted in 50% inhibition of GEO cells AIG, whereas the use of each AS S-Oligo at a 1 or 2 μM concentration resulted respectively in about 10 and 20% growth inhibition. A combination of the three AS S-oligos was even more effective, resulting in about 60% inhibition of GEO cells AIG at a concentration of 1 μM each (3 μM total concentration). The AS S-oligos were also able to inhibit specifically the expression of either AR, CR, or TGF-α proteins in GEO cells, as assessed using immunocytochemistry or Western blot analysis. Finally, a supraadditive growth inhibitory effect of the AS S-oligos and an epidermal growth factor receptor-blocking antibody (monoclonal antibody 528) was observed. These data suggest that the use of a combination of AS S-oligos directed against different growth factors and antibodies directed against their receptors might result in an efficient inhibition of colon carcinoma cell growth.

Original languageEnglish
Pages (from-to)601-609
Number of pages9
JournalClinical Cancer Research
Volume2
Issue number3
Publication statusPublished - Mar 1996

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Normanno, N., Bianco, C., Damiano, V., De Angelis, E., Selvam, M. P., Grassi, M., Magliulo, G., Tortora, G., Bianco, A. R., Mendelsohn, J., Salomon, D. S., & Ciardiello, F. (1996). Growth inhibition of human colon carcinoma cells by combinations of anti-epidermal growth factor-related growth factor antisense oligonucleotides. Clinical Cancer Research, 2(3), 601-609.