Winczyk Katarzyna, Lawnicka Hanna, Pawlikowski Marek, Kunert-Radek Jolanta, Karasek Michal
Department of Neuroendocrinology, Chair of Endocrinology, Medical University of Lodz, Poland.
Neuro Endocrinol Lett. 2006 Jun;27(3):351-4.
Melatonin may influence directly tumor cells through the specific binding sites. The best known melatonin binding sites are membrane receptors. Recently, the participation of nuclear signalling via estrogen as well as RZR/ROR receptors in oncostatic action of melatonin on the breast cancer has been widely discussed. The aim of present study was to investigate effects of melatonin, the selective ligand for nuclear RZR/ROR receptors - CGP 52608, and methotrexate on growth of murine 16/C breast cancer cells.
The experiment was performed in vitro. The breast cancer cells were incubated for 2 days in the presence of melatonin, CGP 52608 (at concentrations of 10(-5)M, 10(-7)M, 10(-9)M, 10-(11)M ) and methotrexate (at concentrations of 0.25 and 0.125 microg/ml). The growth of cells was measured using the modified Mossman method.
All examined compounds significantly inhibited the growth of cancer cells. The effects of MLT and CGP 52 608 were comparable with suppression caused by methotrexate. The significant differences of efficacy between two examined concentrations of methotrexate were not observed.
The obtained data together with our previous results indicate that nuclear receptors RZR/ROR play an important, although not sufficiently recognized role in the oncostatic action of melatonin.
褪黑素可能通过特异性结合位点直接影响肿瘤细胞。最知名的褪黑素结合位点是膜受体。最近,关于雌激素以及RZR/ROR受体介导的核信号传导在褪黑素对乳腺癌的抑癌作用中的参与情况已被广泛讨论。本研究的目的是探讨褪黑素、核RZR/ROR受体的选择性配体——CGP 52608以及甲氨蝶呤对小鼠16/C乳腺癌细胞生长的影响。
实验在体外进行。将乳腺癌细胞在褪黑素、CGP 52608(浓度分别为10⁻⁵M、10⁻⁷M、10⁻⁹M、10⁻¹¹M)和甲氨蝶呤(浓度分别为0.25和0.125μg/ml)存在的情况下培养2天。使用改良的莫斯曼方法测量细胞生长。
所有检测的化合物均显著抑制癌细胞的生长。褪黑素和CGP 52608的作用与甲氨蝶呤引起的抑制作用相当。未观察到两种检测浓度的甲氨蝶呤在疗效上的显著差异。
获得的数据与我们之前的结果共同表明,核受体RZR/ROR在褪黑素的抑癌作用中发挥着重要作用,尽管尚未得到充分认识。