Cappelletti V, Miodini P, Fioravanti L, Di Fronzo G
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Anticancer Res. 1995 Nov-Dec;15(6B):2551-5.
Reports about the effects of progestins on cell proliferation are contradictory. We investigated the effect of progesterone, medroxyprogesterone acetate, megestrol acetate, ORG 2058 and the antiprogestin RU 486 on two hormone-dependent cell lines, T47D and MCF-7 (characterized by a different content of PgR). The aim of the study was to understand the eventual ability of progestins to interfere with cell proliferation stimulated by estradiol and various growth factors (TGF-a, IGF-I, IGF-II).
MCF-7 and T47D cells were maintained in DMEM/F12 medium supplemented with 2% FCS while experiments were carried out in the same culture medium using DCC-stripped FCS.
In the absence of estradiol, all tested progestins generally tended to stimulate cell growth in the T47D cell line, but in the MCF-7 cell line only the highest concentrations (10(-6) M and 10(-7) M) were found to be stimulatory. In contrast, in the presence of 10(-8) M estradiol, progestins tended to inhibit cell growth stimulation in MCF-7 and T47D cell lines. The antiprogestin RU 486 exerted a stimulatory effect similar to that promoted by estradiol itself in MCF-7 cells. Instead, in T47D cells, RU 486 did not modify cell growth in the absence of estradiol, but tended to counteract the estradiol-promoted cell proliferation. In MCF-7 cells, medroxyprogesterone acetate and megestrol acetate were also able to effectively counteract the cell growth induced by TGF-alpha. However, none of these progestins was able to abolish cell proliferation promoted by IGF-I or IGF-II.
We therefore concluded that failure to respond to progestin treatment may be due to the very heterogeneous nature of human breast tumors and to the inability of these molecules to interfere with the IGF-R pathway.
关于孕激素对细胞增殖影响的报道相互矛盾。我们研究了孕酮、醋酸甲羟孕酮、醋酸甲地孕酮、ORG 2058和抗孕激素RU 486对两种激素依赖性细胞系T47D和MCF-7（其特征为孕酮受体含量不同）的影响。本研究的目的是了解孕激素最终干扰由雌二醇和各种生长因子（转化生长因子-α、胰岛素样生长因子-I、胰岛素样生长因子-II）刺激的细胞增殖的能力。
MCF-7和T47D细胞在补充有2%胎牛血清的DMEM/F12培养基中培养，而实验在使用经葡聚糖凝胶柱层析去除类固醇的胎牛血清的相同培养基中进行。
在无雌二醇的情况下，所有测试的孕激素通常倾向于刺激T47D细胞系中的细胞生长，但在MCF-7细胞系中，仅发现最高浓度（10⁻⁶M和10⁻⁷M）具有刺激作用。相反，在存在10⁻⁸M雌二醇的情况下，孕激素倾向于抑制MCF-7和T47D细胞系中的细胞生长刺激。抗孕激素RU 486在MCF-7细胞中发挥了类似于雌二醇本身促进的刺激作用。相反，在T47D细胞中，在无雌二醇的情况下RU 486不改变细胞生长，但倾向于抵消雌二醇促进的细胞增殖。在MCF-7细胞中，醋酸甲羟孕酮和醋酸甲地孕酮也能够有效抵消由转化生长因子-α诱导的细胞生长。然而，这些孕激素均不能消除由胰岛素样生长因子-I或胰岛素样生长因子-II促进的细胞增殖。
因此，我们得出结论，对孕激素治疗无反应可能是由于人类乳腺肿瘤的异质性以及这些分子无法干扰胰岛素样生长因子受体途径。
