PROGESTERONE ANTAGONIST ZK-98.299 (ONAPRISTONE) INHIBITS GROWTH OF THE ESTROGEN-RECEPTOR (ER) AND PROGESTERONE-RECEPTOR (PR) POSITIVE BREAST-CANCER CELL-LINE MCF-7

The antiproliferative effect of the antigestagene ZK 98.299 (Onapristo ne) on the growth of the estrogen receptor (ER) and progesterone recep tor (PR) positive human breast cancer cell line MCF-7 wild type, the E R and PR positive subclone MCF-7M1 and the ER and PR negative breast c ancer cell line MDA-MB 231 has been investigated. Several malignant co ntrol cell lines derived from colon carcinoma, gastric carcinoma and r enal cortical carcinoma were also included in the analysis. Three diff erent concentrations of ZK 98.299 (10(-5)M, 10(-7)M, and 10(-9)M) were used. A dose-dependent growth inhibition (% of control) of MCF7 wild type (10(-5)M: 34.9%; 7M: 72.5%; 10(-9)M: 76.7%) and MCF-7M1 (10(-5)M: 41.9%; 10(-7)M: 89.9%) cell lines, but not of MDA-MB 231 (10(-5)M: 87 .8%; 10(-7)M: 94,2%; 10(-9)M: 100,3%) or other control cell lines was observed, After termination of ZK 98.299 treatment cell proliferation reached control levels. ER and PR control was determined by ER-ICA and PR-ICA (Abbott) immunostaining. Staining intensity was quantitated wi th an image analysis system (CAS) and showed a PR down-regulation in M CF-7 wild type and MCF-7M1 cells treated with ZK 98.299 at 10(-5)M and 10(-7)M, while there was no effect on the ER. In conclusion ZK 98.299 showed an inhibitory effect on the proliferation of the ER and PR pos itive cell line MCF-7, and might be a useful addition to the endocrine treatment modalities available for breast cancer.