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Annals of Oncology 11:319-325, 2000
© 2000 European Society for Medical Oncology

research-article

EGF-related antisense oligonucleotides inhibit the proliferation of human ovarian carcinoma cells

A. Casamassimi1, A. De Luca1, S. Agrawal2, K. Stromberg3, D. S. Salomon4 and N. Normanno1,

1Novel Therapeutic Approaches Section - Oncologia Spenmentale D, ITN-Fondazione Pascale Napoli, Italy
2Hybridon Inc. Cambridge, Massachusetts
3Tumor Growth Factor Section, LTIB, NCI, NIH
4DCB, CBER, FDA Bethesda, Maryland, USA

Correspondence to: N. Normanno, MD Oncologia Sperimentale D ITN-Fondazione Pascale, 80131 Naples, Italy E-mail: nicnorm{at}yahoo.com

Background: The epidermal growth factor (EGF)-like pepti-des CRIPTO (CR), amphiregulin (AR) and transforming growth factor {alpha} (TGF{alpha}) are expressed in human ovarian carcinomas.

Materials and methods: The expression of AR, CR and TGF{alpha} in ovarian carcinoma cell lines was assessed by immuno-cytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The antiproliferative effects of antisense phosphorothioate oligodeoxynucleotides (AS S-Oligos) directed against either AR, CR or TGF{alpha} was evaluated by using a clonogenic assay.

Results: A majority of the ovarian carcinoma cell lines was found to express TGF{alpha}, AR and CR mRNAs and proteins. AS S-Oligos directed against either AR, CR or TGF{alpha} were able to inhibit the anchorage-independent growth of NIH:OVCAR3 and NIH:OVCAR8 cells in a dose dependent manner. A 30%–50% growth inhibition was observed at a 2 µM concentration of the AS S-Oligos. Treatment of these cells with combinations of EGF-related AS S-Oligos resulted in a more significant growth inhibition when compared to treatment with a single AS S-oligo. A 60%–75% growth inhibition was observed using combinations of AR, CR and TGF{alpha} AS S-oligos at a total concentration of 2 µM. An additive growth-inhibitory effect occurred when ovarian carcinoma cells were exposed to the AS S-Oligos after treatment with either paclitaxel or cis-platinum.

Conclusions: These data suggest that EGF-related peptides function as autocrine growth factors in ovarian carcinoma cells, and that they might represent targets for experimental therapy of ovarian carcinoma.

antisense oligonucleotides, EGF-related peptides, ovarian carcinoma


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