Growth inhibition of cervix carcinoma cells in vivo by endothelin A receptor blockade.
In human papillomavirus (HPV)-positive cervical cancer cells, the endothelin A receptor (ET(A)R) 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(A)R. In nude mice, the ET(A)R-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.
Bagnato
Anna
A
Laboratoryies of Molecular Pathology and Ultrastructure, Regina Elena Cancer Institute, Rome, Italy.
Cirilli
Alessia
A
Salani
Debora
D
Simeone
Paola
P
Muller
Antonio
A
Nicotra
Maria Rita
MR
Natali
Pier Giorgio
PG
Venuti
Aldo
A
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D000077868:Atrasentan; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D065128:Endothelin Receptor Antagonists; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D017239:Paclitaxel; D000077868:Atrasentan