Inhibition of tumour growth in vivo and in vitro by prostaglandin E

Abstract

PROSTAGLANDIN E (PGE), both endogenous and exogenous, has been shown to inhibit significantly the rates of tumour-cell proliferation in vitro^1–4 .Suppression of PG biosynthesis with indomethacin^5,6 resulted in stimulation of cell replication, an effect which was readily reversed by the addition to the medium of small amounts of exogenous PGE₁ (10 ng ml⁻¹) (ref. 5). Corticosteroids have recently been shown to inhibit the biosynthesis of PGE by rheumatoid synovia⁷ and mouse fibro-sarcoma HSDM₁ (ref. 8) in vitro; the mechanism of this action seems to be by interfering with the release of arachidonic acid from phospholipids⁹. To evaluate further the possible role of PGE in the control of tumour-cell proliferation, we have studied the effects of hydrocortisone and indomethacin on the growth rate of B-16 mouse melanoma in vitro. The studies demonstrate that both compounds cause significant stimulation of tumour-cell replication in vitro, associated with inhibition of PG biosynthesis, albeit by two different mechanisms. In addition, we have extended the observations on the effects of exogenous PGE1, by demonstrating that subcutaneous administration of 16,16-dimethyl-PGE₂-methyl ester significantly inhibits tumour growth in vivo.