Modulation of growth, prostaglandin synthesis, and prolactin-binding in two cultured rat mammary carcinoma cell lines by flurbiprofen.
The effect of treatment with flurbiprofen (FB), a non-steroidal anti-inflammatory drug, on growth, prostaglandin synthesis, and prolactin receptor levels was examined in two established rat mammary carcinoma cell lines. Growth of NMU cells was suppressed with a concentration of 1 microgram FB/ml culture medium (4 x 10(-5) M); RBA cells, in contrast, were less sensitive, being inhibited only by a 100 micrograms/ml (4 x 10(-4) M) concentration of the drug. Prostaglandin (PG) synthesis by both cells lines, as indicated by decreased release of PGE2 and PGF2 alpha into the culture medium, was inhibited by 0.1, 1 and 10 micrograms/ml of FB. Both carcinoma cell lines exhibited high levels of specific prolactin receptors (PRLR) (9-11,000 sites/cell); binding was diminished in cells exposed to 1 microgram/ml (4 x 10(-6) M), and abolished completely by 10 micrograms/ml (4 x 10(-5) M) of FB. In marked contrast to the results at higher concentrations, at 0.1 microgram/ml (4 x 10(-7) M), the drug caused a significant increase in the prolactin binding capacity of RBA cells and a diminution in PG production, but in the absence of any measurable effect on cell proliferation. A similar, but less pronounced trend was seen in the NMU cell line. When NMU cells were cultured in the presence of 10 micrograms/ml FB for 4 days, and then in inhibitor-free medium for a further 3 days, recovery of growth was demonstrated, together with the reappearance of prolactin-binding capacity. The effect of FB on RBA cell PRLR expression was also reversible, though concomitant changes in cell growth were less obvious. Hence, the inhibitory effect of FB on PG synthesis, and the associated decrease in prolactin binding capacity, was specific and reversible and not the result of a generalized toxic effect.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D013006:Growth Hormone / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D011388:Prolactin / Q000378:metabolism*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011981:Receptors, Prolactin; D012756:Sheep
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D011448:Prostaglandin Antagonists; D011956:Receptors, Cell Surface; D011981:Receptors, Prolactin; D011388:Prolactin; D013006:Growth Hormone