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  • Original Paper
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Simultaneous blockade of different EGF-like growth factors results in efficient growth inhibition of human colon carcinoma xenografts

Oncogene volume 19, pages 5863–5871 (2000)Cite this article

Abstract

A majority of human colon carcinomas coexpress the epidermal growth factor (EGF)-related peptides transforming growth factor α (TGFα), amphiregulin (AR) and CRIPTO-1 (CR). We have synthesized novel, antisense mixed backbone oligonucleotides (AS MBOs) directed against TGFα, AR and CR. We screened the EGF-related AS MBOs for their ability to inhibit the anchorage independent growth of GEO human colon carcinoma cells. The MBOs that showed a high in vitro efficacy were then used for in vivo experiments. TGFα, AR and CR AS MBOs were able to inhibit the growth of GEO tumor xenografts in nude mice in a dose-dependent manner. Furthermore, the AS MBOs were able to specifically inhibit the expression of the target mRNAs and proteins in the tumor xenografts. A more significant tumor growth inhibition was observed when mice were treated with a combination of the three AS MBOs as compared to treatment with a single AS MBO. Finally, tumors from mice treated with TGFα, AR and CR AS MBOs showed a significant reduction of microvessel count, as compared with tumors from untreated mice or from mice treated with a single AS MBO. These data suggest that combinations of AS oligonucleotides directed against different growth factors might represent a novel, experimental therapy approach of colon carcinomas.

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Acknowledgements

This work was supported in part by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) from the Italy-USA Program on Therapy of Tumors and from the Italian Department of Health (ICS150.1/RF 99.8) to N Normano. The authors thank Hybridon Inc. (Cambridge, MA, USA) for providing the antisense oligonucleotides that have been used in this work.

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Authors and Affiliations

  1. Novel Therapeutic Approaches Section – Oncologia Sperimentale D, ITN-Fondazione Pascale, Naples, 80131, Italy

    Antonella De Luca, Amelia Casamassimi & Nicola Normanno

  2. Animal Facility, ITN-Fondazione Pascale, Naples, 80131, Italy

    Claudio Arra & Paola Ferraro

  3. Anatomia Patologica ULSS 3, 36061 Bassano del Grappa (VI), Italy

    Antonio D'Antonio

  4. Anatomia Patologica, ITN-Fondazione Pascale, Naples, 80131, Italy

    Simona Losito

  5. Cattedra di Oncologia Medica, Dip. di Endocrinologia e Oncologia Molecolare e Clinica, Università Federico II, Napoli, 80131, Italy

    Fortunato Ciardiello

  6. Tumor Growth Factor Section, LTIB, NCI, NIH, Bethesda, 20892, Maryland, USA

    David S Salomon

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  1. Antonella De Luca
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De Luca, A., Arra, C., D'Antonio, A. et al. Simultaneous blockade of different EGF-like growth factors results in efficient growth inhibition of human colon carcinoma xenografts. Oncogene 19, 5863–5871 (2000). https://doi.org/10.1038/sj.onc.1203979

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