Simultaneous blockage of different EGF-like growth factors results in efficient growth inhibition of human colon carcinoma xenografts.

Abstract	A majority of human colon carcinomas coexpress the epidermal growth factor (EGF)-related peptides transforming growth factor alpha (TGFalpha), amphiregulin (AR) and CRIPTO-1 (CR). We have synthesized novel, antisense mixed backbone oligonucleotides (AS MBOs) directed against TGFalpha, 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. TGFalpha, 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 TGFalpha, 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.
Authors	A De Luca, C Arra, A D'Antonio, A Casamassimi, S Losito, P Ferraro, F Ciardiello, D S Salomon, N Normanno
Journal	Oncogene (Oncogene) Vol. 19 Issue 51 Pg. 5863-71 (Nov 30 2000) ISSN: 0950-9232 [Print] England
PMID	11127817 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	AREG protein, human Amphiregulin Areg protein, mouse EGF Family of Proteins GPI-Linked Proteins Glycoproteins Growth Inhibitors Growth Substances Intercellular Signaling Peptides and Proteins Membrane Glycoproteins Neoplasm Proteins Oligonucleotides, Antisense TDGF1 protein, human Tdgf1 protein, mouse Thionucleotides Transforming Growth Factor alpha Epidermal Growth Factor
Topics	Amphiregulin Animals Colonic Neoplasms (drug therapy, metabolism, pathology) EGF Family of Proteins Epidermal Growth Factor GPI-Linked Proteins Glycoproteins (antagonists & inhibitors, biosynthesis, genetics) Growth Inhibitors (genetics, pharmacology) Growth Substances (biosynthesis, genetics) Humans Intercellular Signaling Peptides and Proteins Membrane Glycoproteins Mice Mice, Nude Neoplasm Proteins (antagonists & inhibitors, biosynthesis, genetics) Neovascularization, Pathologic (drug therapy) Oligonucleotides, Antisense (genetics, pharmacology) Thionucleotides (genetics, pharmacology) Transforming Growth Factor alpha (antagonists & inhibitors, biosynthesis, genetics) Tumor Cells, Cultured Xenograft Model Antitumor Assays

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