Vaccine Research Institute of San Diego, 3030 Bunker Hill Street, Suite 200, San Diego, CA, 92109, USA.
Pellficure Pharmaceuticals, Inc., 2325 Camino del Collado, La Jolla, CA, 92037, USA.
Sci Rep. 2018 Feb 9;8(1):2694. doi: 10.1038/s41598-018-20451-9.
Treatment of mice harboring PTEN-P2 tumors in the prostate or on prostate tissue in vivo with 5-hydroxy-2-methyl-1,4-naphthoquinone, also known as plumbagin, results in tumor regression in castrated mice, but not in intact mice. This suggested that dihydrotestosterone (DHT) production in the testes may prevent cell death due to plumbagin treatment, but the underlying mechanism is not understood. We performed RNA-seq analysis on cells treated with combinations of plumbagin and DHT, and analyzed differential gene expression, to gain insight into the interactions between androgen and plumbgin. DHT and plumbagin synergize to alter the expression of many genes that are not differentially regulated by either single agent when used alone. These experiments revealed that, for many genes, increases in mRNAs caused by DHT are sharply down-regulated by plumbagin, and that many transcripts change in response to plumbagin in a DHT-dependent manner. This suggests that androgen receptor mediates some of the effects of plumbagin on gene expression.
用 5-羟基-2-甲基-1,4-萘醌（也称为白花丹醌）治疗前列腺中携带 PTEN-P2 肿瘤或前列腺组织中的荷瘤小鼠，可导致去势小鼠的肿瘤消退，但不能导致完整小鼠的肿瘤消退。这表明睾丸中双氢睾酮（DHT）的产生可能阻止了由于白花丹醌治疗引起的细胞死亡，但潜在机制尚不清楚。我们对用白花丹醌和 DHT 联合处理的细胞进行了 RNA-seq 分析，并分析了差异基因表达，以深入了解雄激素和白花丹醌之间的相互作用。DHT 和白花丹醌协同作用，改变了许多基因的表达，而这些基因在单独使用任一药物时都不会受到差异调控。这些实验表明，对于许多基因，DHT 引起的 mRNA 增加被白花丹醌急剧下调，并且许多转录本以 DHT 依赖的方式响应白花丹醌而变化。这表明雄激素受体介导了白花丹醌对基因表达的一些影响。
