Fischer T W, Zmijewski M A, Zbytek B, Sweatman T W, Slominski R M, Wortsman J, Slominski A
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, 38163, USA.
Int J Oncol. 2006 Sep;29(3):665-72. doi: 10.3892/ijo.29.3.665.
Melatonin has been shown to have oncostatic effects on malignant melanoma in vitro and in vivo. We studied the growth suppressive effects of melatonin over a wide range of concentrations in four melanoma cell lines (SBCE2, WM-98, WM-164 and SKMEL-188) representative for different growth stages and phenotype. Melanoma cells were incubated with melatonin 10(-12)-10(-3) M, and proliferation and clonogenicity was assessed at 12 h and 14 days, respectively. We also determined the expression of cytosolic quinone oxidoreductases NQO1, NQO2 (known as MT3 receptor) and nuclear receptor RORalpha by RT-PCR. Melatonin at pharmacological concentrations (10(-3)-10(-7) M) suppressed proliferation in all melanoma cell lines. In SKMEL-188 cells cultured in serum-free media, melatonin at low concentrations (10(-12)-10(-10) M) also slightly attenuated the proliferation. The effects of pharmacological doses of melatonin were confirmed in the clonogenic assay. Expression of NQO1 was detected in all cell lines, whereas NQO2 and nuclear receptor RORalpha including its isoform RORalpha4 were present only in SBCE2, WM-164 and WM-98. Thus, melatonin differentially suppressed proliferation in melanoma cell lines of different behaviour. The intensity of the oncostatic response to melatonin could be related to the cell-line specific pattern of melatonin cellular receptors and cytosolic binding protein expression.
褪黑素已被证明在体外和体内对恶性黑色素瘤具有抑癌作用。我们研究了褪黑素在广泛浓度范围内对四种代表不同生长阶段和表型的黑色素瘤细胞系（SBCE2、WM - 98、WM - 164和SKMEL - 188）的生长抑制作用。将黑色素瘤细胞与10(-12)-10(-3)M的褪黑素孵育，分别在12小时和14天时评估细胞增殖和克隆形成能力。我们还通过逆转录聚合酶链反应（RT-PCR）测定了胞质醌氧化还原酶NQO1、NQO2（也称为MT3受体）和核受体RORα的表达。药理浓度（10(-3)-10(-7)M）的褪黑素抑制了所有黑色素瘤细胞系的增殖。在无血清培养基中培养的SKMEL - 188细胞中，低浓度（10(-12)-10(-10)M）的褪黑素也轻微减弱了细胞增殖。褪黑素药理剂量的作用在克隆形成试验中得到证实。所有细胞系中均检测到NQO1的表达，而NQO2和核受体RORα包括其异构体RORα4仅存在于SBCE2、WM - 164和WM - 98中。因此，褪黑素对不同行为的黑色素瘤细胞系增殖的抑制作用存在差异。褪黑素抑癌反应的强度可能与褪黑素细胞受体和胞质结合蛋白表达的细胞系特异性模式有关。
