Winczyk Katarzyna, Fuss-Chmielewska Julita, Lawnicka Hanna, Pawlikowski Marek, Karasek Michal
Department of Neuroendocrinology, Chair of Endocrinology, Medical University of Lodz, Poland.
Neuro Endocrinol Lett. 2009;30(5):657-62.
Our earlier studies have shown that MLT exerts the inhibitory effect on murine cancer via membrane and nuclear receptors. We have found that the antagonist of MT1 receptors does not diminish the antiproliferative effect of MLT on Colon 38 cells, and the contribution of MT2 receptors has been suggested to be responsible. Therefore, in the present study we have examined the influence of the 4-phenyl-2-propionamidotetralin (4P-PDOT), which is a selective antagonist of MT2 membrane receptor, and luzindole - an antagonist of both membrane receptors, on an oncostatic action of MLT.
The murine cancer cell line Colon 38 was used in the experiments. In 48 hrs cell culture the effects of MLT, 4P-PDOT and luzindole administered alone and MLT applied jointly with either 4P-PDOT or luzindole were examined. The growth of cancer cells was assessed using the modified colorimetric Mosmann method.
Melatonin at both examined concentrations (10-7, 10-9 M) significantly decreased the viability of cancer cells. The selective antagonist of MT2 membrane receptor, namely 4P-PDOT and luzindole applied separately did not have an effect on the growth of Colon 38 cells. The addition of 4P-PDOT to MLT did not change the inhibitory effect of MLT, whereas luzindole given together with MLT diminished, but failed to block totally, the oncostatic properties of MLT.
The obtained data and our previous studies conducted on Colon 38 cancer indicate that membrane melatonin receptors are not indispensable to the oncostatic action of melatonin and thus other pathways such as nuclear signaling and receptor-independent mechanism may be also involved.
我们早期的研究表明，褪黑素（MLT）通过膜受体和核受体对小鼠癌症发挥抑制作用。我们发现MT1受体拮抗剂并不会减弱MLT对结肠38细胞的抗增殖作用，因此推测MT2受体起了作用。所以，在本研究中，我们检测了MT2膜受体的选择性拮抗剂4-苯基-2-丙酰胺基四氢萘（4P-PDOT）以及膜受体拮抗剂鲁辛朵对MLT抑癌作用的影响。
实验采用小鼠癌细胞系结肠38。在48小时的细胞培养中，检测单独给予MLT、4P-PDOT和鲁辛朵以及MLT与4P-PDOT或鲁辛朵联合使用的效果。使用改良的比色法（Mosmann法）评估癌细胞的生长情况。
在所检测的两种浓度（10⁻⁷、10⁻⁹ M）下，褪黑素均显著降低了癌细胞的活力。单独应用MT2膜受体的选择性拮抗剂4P-PDOT和鲁辛朵对结肠38细胞的生长没有影响。在MLT中添加4P-PDOT并没有改变MLT的抑制作用，而与MLT一起给予鲁辛朵则减弱了但并未完全阻断MLT的抑癌特性。
所获得的数据以及我们之前对结肠38癌进行的研究表明，膜褪黑素受体对于褪黑素的抑癌作用并非不可或缺，因此可能还涉及其他途径，如核信号传导和非受体依赖机制。
