Lama G, Angelucci C, Bruzzese N, Iacopino F, Nori S L, D'Atri S, Turriziani M, Bonmassar E, Sica G
Istituto di Istologia ed Embriologia, Università Cattolica del Sacro Cuore, Rome, Italy.
Melanoma Res. 1998 Aug;8(4):313-22. doi: 10.1097/00008390-199808000-00004.
We investigated the effect of oestrogens, anti-oestrogens and flavonoids on the growth of a human melanoma cell line (SK-Mel-28) and, at the same time, the presence of both type I oestrogen receptors (ERs) and type II oestrogen binding sites (type II EBS) to gain a fuller picture of the relationship between melanoma cell proliferation and receptor status. 17beta-Oestradiol (E2) and the flavonoid quercetin (Q) produced a marked inhibition of proliferation, but only at the highest dose used (10(-5) M) and only when added daily to the medium. Diethylstilboestrol (DES) (10(-5) M) was effective in inhibiting cell growth when the medium was renewed every 3 days and produced a more pronounced reduction when added daily to the medium. Tamoxifen (TAM) inhibited cell proliferation at a dose starting from 10(-7) M when the medium was renewed every 3 days. When added daily to the medium, it did not induce a greater inhibitory effect and it was cytotoxic at 5 x 10(-6) M and 10(-5) M. The antiproliferative effect of E2, DES and Q did not seem to be dependent on their interaction with ERs, which were minimally detected in SK-Mel-28 in both immunocytochemical and biochemical assays. Our model revealed, through a biochemical assay, a large number of type II EBSs which could be involved in the anti-oestrogen action, but this does not exclude the involvement of other mechanisms. Finally, TAM (10(-5) M) appeared to reduce the activity of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase, an effect that could be interesting from the point of view of the therapeutic efficacy of alkylating agents.
我们研究了雌激素、抗雌激素和类黄酮对人黑色素瘤细胞系（SK-Mel-28）生长的影响，同时研究了I型雌激素受体（ERs）和II型雌激素结合位点（II型EBS）的存在情况，以更全面地了解黑色素瘤细胞增殖与受体状态之间的关系。17β-雌二醇（E2）和类黄酮槲皮素（Q）仅在所用最高剂量（10⁻⁵ M）且每天添加到培养基中时才对增殖产生显著抑制作用。己烯雌酚（DES）（10⁻⁵ M）在每3天更换一次培养基时可有效抑制细胞生长，每天添加到培养基中时抑制作用更明显。他莫昔芬（TAM）在每3天更换一次培养基时，从10⁻⁷ M的剂量开始就能抑制细胞增殖。每天添加到培养基中时，它不会产生更大的抑制作用，并且在5×10⁻⁶ M和10⁻⁵ M时具有细胞毒性。E2、DES和Q的抗增殖作用似乎不依赖于它们与ERs的相互作用，在SK-Mel-28细胞的免疫细胞化学和生化检测中均未检测到ERs。我们的模型通过生化检测发现了大量可能参与抗雌激素作用的II型EBS，但这并不排除其他机制的参与。最后，TAM（10⁻⁵ M）似乎降低了DNA修复酶O6-烷基鸟嘌呤-DNA烷基转移酶的活性，从烷化剂治疗效果的角度来看，这一作用可能很有意思。
