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Growth Inhibition of Cervix Carcinoma Cells in Vivo by Endothelin A Receptor Blockade¹

Laboratories of Virology [A. C., P. S., A. M., A. V.], Molecular Pathology and Ultrastructure [A. B., D. S.], Immunology [P. G. N.], Regina Elena Cancer Institute, and Biotechnology Department Consiglio Nazionale delle Richerche [M. R. N.], 00158 Rome, Italy

In human papillomavirus (HPV)-positive cervical cancer cells, the endothelin A receptor (ET_AR) mediates an endothelin-1-induced mitogenic effect, thus representing a relevant target for antitumor therapy. Here, we describe the complete inhibition of human cervix carcinoma growth by blocking the ET_AR. In nude mice, the ET_AR-selective antagonist atrasentan inhibits the growth and the neoangiogenesis of cervical carcinoma cell xenografts. Two cycles of treatment completely revert tumor growth. Atrasentan displays additive effects when administered in combination with the cytotoxic drug paclitaxel. These results demonstrate that by inhibiting cell proliferation and angiogenesis, this small molecule may help to control cervical cancer by either monotherapy or combination therapy.

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