Yang Quan-Hui, Xu Jian-Ning, Xu Rong-Kun, Pang Shiu-Fun
Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
J Pineal Res. 2007 Mar;42(2):172-9. doi: 10.1111/j.1600-079X.2006.00403.x.
Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the growth of pituitary prolactin-secreting tumor cells. Primary cultured prolactinoma cells from E(2)-induced rat pituitary prolactin-secreting tumor were treated with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days. Apoptosis was evaluated using flow cytometry and the TdT-mediated dUTP nick-end labeling (TUNEL) method. In addition, cell viability was analyzed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that incubation of prolactinoma cells with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days inhibited cell growth and increased cell apoptosis. Furthermore, melatonin increased caspase-3 activity, Bax mRNA expression, and cytochrome c protein expression. Conversely, Bcl-2 mRNA expression and mitochondrial membrane potential were inhibited by melatonin treatment. Our results further suggest that melatonin inhibits tumor growth by inducing apoptosis of rat pituitary prolactin-secreting tumor directly via the damage of mitochondria.
早期研究表明，褪黑素在体内可抑制17-β-雌二醇（E₂）诱导的大鼠垂体催乳素分泌瘤（催乳素瘤）的生长。通过研究褪黑素对垂体催乳素分泌瘤细胞生长的体外作用，进一步探讨了褪黑素对催乳素分泌瘤的抑制作用机制。用10⁻⁵、10⁻⁴或10⁻³ m的褪黑素处理来自E₂诱导的大鼠垂体催乳素分泌瘤的原代培养催乳素瘤细胞5天。使用流式细胞术和TdT介导的dUTP缺口末端标记（TUNEL）法评估细胞凋亡。此外，通过（3,4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）法分析细胞活力。结果发现，用10⁻⁵、10⁻⁴或10⁻³ m的褪黑素处理催乳素瘤细胞5天可抑制细胞生长并增加细胞凋亡。此外，褪黑素增加了半胱天冬酶-3活性、Bax mRNA表达和细胞色素c蛋白表达。相反，褪黑素处理可抑制Bcl-2 mRNA表达和线粒体膜电位。我们的结果进一步表明，褪黑素通过直接损伤线粒体诱导大鼠垂体催乳素分泌瘤细胞凋亡来抑制肿瘤生长。
