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Anti‐sense oligonucleotides directed against EGF‐related growth factors enhance anti‐proliferative effect of conventional anti‐tumor drugs in human colon‐cancer cells
Author(s) -
De Luca Antonella,
Selvam Mouna P.,
Sandomenico Claudia,
Pepe Stefano,
Bianco A. Raffaele,
Ciardiello Fortunato,
Salomon David S.,
Normanno Nicola
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971009)73:2<277::aid-ijc19>3.0.co;2-c
Subject(s) - clonogenic assay , amphiregulin , cell growth , cancer research , growth inhibition , epidermal growth factor , oligonucleotide , growth factor , pharmacology , cell cycle , cell , biology , medicine , microbiology and biotechnology , receptor , biochemistry , dna
Abstract We have demonstrated that anti‐sense phosphorothioate oligodeoxynucleotides (AS S‐oligos) directed against the EGF‐like growth factors CRIPTO (CR), amphiregulin (AR) or transforming‐growth‐factor‐α(TGFα) mRNA, are equipotent in their ability to inhibit the growth of human colon‐carcinoma GEO cells. In this study, we evaluated the effect of combinations of these AS S‐oligos and conventional anti‐tumor drugs, such as 5‐fluorouracil (5‐FU), adriamycin (ADR), mitomycin C (MIT) and cis‐platinum (CDDP), on GEO cell growth. Dose‐dependent growth inhibition was observed by treatment either with AS S‐oligos or with anti‐tumor drugs, using a clonogenic assay. Furthermore, an additive growth‐inhibitory effect occurred when GEO cells were exposed to the AS S‐oligos after treatment with different concentrations of either 5‐FU, MIT, ADR or CDDP. For example, treatment of GEO cells with a combination of low concentrations of 5‐FU and any of the 3 AS S‐oligos resulted in up to 70% growth inhibition. However, treatment of GEO cells with AS S‐oligos before exposure to 5‐FU or CDDP resulted in reduced efficacy of both drugs. Flow‐cytometric analysis of DNA content demonstrated that treatment with the AS S‐oligos caused a slight reduction of the percentage of cells in the S‐phase of the cell cycle. These data suggest that combinations of AS S‐oligos directed against EGF‐related growth factors and of conventional anti‐tumor drugs may result in efficient inhibition of colon‐carcinoma cell growth. Int. J. Cancer 73:277–282, 1997. © 1997 Wiley‐Liss, Inc.