Response of human ovarian carcinoma cell lines to antiprogestin mifepristone.
The effects of antiprogestin mifepristone (MF) on the growth, progesterone receptor expression and cell cycle kinetics of several human ovarian epithelial carcinoma (OEC) cell lines were evaluated. MF, a synthetic antiprogestin, has been shown to have some antiproliferative activity in breast tumors and in the endometrium, but its efficacy in ovarian carcinomas has not been explored previously. Continuous exposure of OEC cells to MF resulted in a dose- and time-dependent growth inhibition, as determined by MTT assay. Growth inhibition was apparent by day three following addition of MF to cultures in vitro. All cell lines used in this study expressed a progesterone receptor (PR). MF down regulated PR expression on these cells. Changes in the cell cycle kinetics of OEC cells exposed to MF correlated with the observed antiproliferative effects. MF blocked cells in a G0/G1 phase of the cell cycle and thus reduced the number of cells in the S phase. The efficacy of MF was compared with that of taxol and tamoxifen in the same human OEC cell lines. Continuous exposure of OEC cells to tamoxifen resulted in a varied cytostatic response and a transient change in the cell cycle. Taxol inhibited growth of some but not all of the cell lines. These results indicate that PR-positive human OEC cells are sensitive to MF in vitro and that MF may be an active agent against ovarian epithelial tumors.
Rose
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University of Medicine and Dentistry of New Jersey, Camden, New Jersey, USA.
Barnea
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ER
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D006727:Hormone Antagonists; D011980:Receptors, Progesterone; D013629:Tamoxifen; D015735:Mifepristone; D017239:Paclitaxel