When orally active high affinity ET-RA antagonist ZD4054, which has no detectable affinity for ET-RB, was applied in vitro, it inhibited ET-1 induced proliferation of human pre-osteoblast cells [21], human ovarian carcinoma cell lines HEY and OVCA 433 [22] and further demonstrated ET-RA was involved in signaling in cancer cell proliferation. This evidence concerns the gene EDN1 and ovarian carcinoma.