Inhibition of tumour growth in vivo and in vitro by prostaglandin E
Inhibition of tumour growth in vivo and in vitro by prostaglandin E
复制标题
前列腺素 E 在体内和体外抑制肿瘤生长
作者：
M. Santoro;Gordon W. Philpott;Bernard M. Jaffe
内源性和外源性前列腺素E（PGE）均能显著抑制体外肿瘤细胞增殖率1 -4。用吲哚美辛抑制PG生物合成5，6可刺激细胞复制，向培养基中加入少量外源性PGE 1（10 ng ml−1）可逆转该效应（参考文献5）。最近，皮质类固醇在体外被证明可抑制类风湿性滑膜7和小鼠纤维肉瘤HSDM 1的PGE生物合成（参考文献8）;该作用的机制似乎是通过干扰花生四烯酸从磷脂中的释放9。为了进一步评价PGE在控制肿瘤细胞增殖中的可能作用，我们研究了氢化可的松和吲哚美辛对体外B-16小鼠黑色素瘤生长速率的影响。研究表明，这两种化合物引起显着的刺激肿瘤细胞的体外复制，与PG生物合成的抑制，虽然通过两种不同的机制。此外，我们已经扩展了对外源性PGE 1的作用的观察，通过证明皮下施用16，16-二甲基-PGE 2-甲酯显著抑制体内肿瘤生长。
PROSTAGLANDIN E (PGE), both endogenous and exogenous, has been shown to inhibit significantly the rates of tumour-cell proliferation in vitro1–4 .Suppression of PG biosynthesis with indomethacin5,6 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.