Johnson D E, Ochieng J, Evans S L
Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA.
Anticancer Drugs. 1995 Jun;6(3):471-4. doi: 10.1097/00001813-199506000-00017.
Dopamine agonists have been indicated as treatment for disorders such as Parkinson's disease, cardiogenic shock and dopamine insufficiency. A unique relationship exists between dopamine and carcinogenicity. Chronic prolactin stimulation has been identified as a promoter of carcinogenicity. Prolactin secretion is regulated through dopamine receptor activation. Dopaminergic agonists inhibit prolactin release and antagonists increase release. High levels of prolactin have been shown to suppress production of estrogen and progesterone. As a result of these findings, a series of experiments were designed to examine the effects of a specific dopamine agonist, SKF 38393, against MCF-7 cells. MDA-MB231 and MCF-10 cells were used as negative controls. The breast cancer in vitro screening procedure involved the plating of MCF-7, MDA-MB231 and MCF-10 cells in a 96-well plate assay. After 1 day, the cells were exposed to SKF 38393 for 2 days and cell growth was determined by the Alamar blue dye reagent method. The optical density data was analyzed and IC50 values determined. The results indicated that SKF 38393 caused a significant decrease in proliferation of MCF-7 cells. The IC50 value was 0.1 +/- 0.03 microM. The results also indicated no significant effect on MDA-MB231 and MCF-10 cells.
多巴胺激动剂已被用作治疗帕金森病、心源性休克和多巴胺分泌不足等疾病。多巴胺与致癌性之间存在独特的关系。慢性催乳素刺激已被确定为致癌性的促进因素。催乳素的分泌通过多巴胺受体激活来调节。多巴胺能激动剂抑制催乳素释放,而拮抗剂则增加其释放。高水平的催乳素已被证明会抑制雌激素和孕激素的产生。基于这些发现,设计了一系列实验来研究特定多巴胺激动剂SKF 38393对MCF-7细胞的影响。MDA-MB231和MCF-10细胞用作阴性对照。乳腺癌体外筛选程序包括在96孔板试验中接种MCF-7、MDA-MB231和MCF-10细胞。1天后,将细胞暴露于SKF 38393中2天,并通过阿拉玛蓝染料试剂法测定细胞生长情况。分析光密度数据并确定IC50值。结果表明,SKF 38393导致MCF-7细胞增殖显著下降。IC50值为0.1±0.03微摩尔。结果还表明,对MDA-MB231和MCF-10细胞没有显著影响。