Mifepristone (RU486) is an orally effective progesterone (PR) receptor and glucocorticoid receptor (GR) antagonist used as an abortion drug with in vitro IC50 values of 0.2nM and 2.6nM, respectively [1]. Mifepristone is an antiprogestin that blocks the effects of progesterone, causing cervical and uterine vasodilation and uterine contractions [2]. Mifepristone can also be used to treat depression and improve neurocognitive function and mood [3].
In vitro, treatment of ovarian cancer SK-OV-3, OV2008, IGROV-1 and OV2008 cells with mifepristone (20μM) completely blocked cell growth at 24h, and the effect lasted for 3 days [4]. Treatment of human gastric adenocarcinoma MKN-45 cells with mifepristone (5, 10, 20μM) dose-dependently inhibited heterotypic adhesion of cells to matrix gel, accompanied by downregulation of integrin β3 expression in cells [5].
In vivo, oral treatment of C57BL/6 mice with mifepristone (200 mg/kg) for 1 week completely blocked the reduction in the CD4:CD8 T cell ratio in secondary lymphoid tissue (SLT) induced by enriched environment (EE)[6]. Mifepristone (25 mg/kg) treated by subcutaneous injection for 14 days in depression model rats improved interleukin 1β (IL-1β)-induced depressive-like behavior and regulated the function of microglia and astrocytes[7].
References:
[1] Jiang W, Allan G, Fiordeliso J J, et al. New progesterone receptor antagonists: phosphorus-containing 11β-aryl-substituted steroids[J]. Bioorganic & medicinal chemistry, 2006, 14(19): 6726-6732.
[2] Ashok P W, Wagaarachchi P T, Templeton A. The antiprogestogen mifepristone: a review[J]. Current Medicinal Chemistry-Immunology, Endocrine & Metabolic Agents, 2002, 2(2): 71-90.
[3] Young A H, Gallagher P, Watson S, et al. Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder[J]. Neuropsychopharmacology, 2004, 29(8): 1538-1545.
[4] Goyeneche A A, Caron R W, Telleria C M. Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo[J]. Clinical Cancer Research, 2007, 13(11): 3370-3379.
[5] Li D Q, Wang Z B, Bai J, et al. Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo[J]. World Journal of Gastroenterology: WJG, 2004, 10(12): 1726.
[6] Xiao R, Bergin S M, Huang W, et al. Environmental and genetic activation of hypothalamic BDNF modulates T-cell immunity to exert an anticancer phenotype[J]. Cancer immunology research, 2016, 4(6): 488-497.
[7] Zhang Y P, Wang H Y, Zhang C, et al. Mifepristone attenuates depression-like changes induced by chronic central administration of interleukin-1β in rats[J]. Behavioural brain research, 2018, 347: 436-445.
Mifepristone (RU486）是一种口服有效的孕酮（PR）受体和糖皮质激素受体（GR）拮抗剂，用作堕胎药物，体外实验中IC50值分别为0.2nM和2.6nM[1]。Mifepristone是一种抗孕激素，它的作用是阻断黄体酮的作用，使子宫颈和子宫血管扩张并引起子宫收缩[2]。 Mifepristone还可用于治疗抑郁症，改善神经认知功能和情绪[3]。
在体外，Mifepristone（20μM）处理卵巢癌SK-OV-3、OV2008、IGROV-1和OV2008细胞，在24h时可完全阻止细胞生长，且效果可持续3天[4]。Mifepristone（5、10、20μM）处理人胃腺癌MKN-45细胞，剂量依赖性地抑制了细胞对基质胶的异型粘附，并伴随着细胞中整合素β3表达的下调[5]。
在体内，Mifepristone（200mg/kg）通过口服治疗C57BL/6小鼠1周，完全阻断了富集环境（EE）诱导的次级淋巴组织（SLT）中CD4：CD8 T细胞比率的降低[6]。Mifepristone（25mg/kg）通过皮下注射治疗抑郁模型大鼠14天，改善了白细胞介素 1β（IL-1β）诱导的抑郁样行为，调节了小胶质细胞和星形胶质细胞的功能[7]。