2-花生四烯酸甘油酯：一种雄激素非依赖性前列腺癌细胞侵袭的新型抑制剂。

2-arachidonoylglycerol: a novel inhibitor of androgen-independent prostate cancer cell invasion.

作者信息

Nithipatikom Kasem, Endsley Michael P, Isbell Marilyn A, Falck John R, Iwamoto Yoshiki, Hillard Cecilia J, Campbell William B

机构信息

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

出版信息

Cancer Res. 2004 Dec 15;64(24):8826-30. doi: 10.1158/0008-5472.CAN-04-3136.

DOI:10.1158/0008-5472.CAN-04-3136

PMID:15604240

Abstract

Endocannabinoids have been implicated in cancer. Increasing endogenous 2-arachidonoylglycerol (2-AG) by blocking its metabolism inhibits invasion of androgen-independent prostate cancer (PC-3 and DU-145) cells. Noladin ether (a stable 2-AG analog) and exogenous CB1 receptor agonists possess similar effects. Conversely, reducing endogenous 2-AG by inhibiting its synthesis or blocking its binding to CB1 receptors with antagonists increases the cell invasion. 2-AG and noladin ether decrease protein kinase A activity in these cells, indicating coupling of the CB1 receptor to downstream effectors. The results suggest that cellular 2-AG, acting through the CB1 receptor, is an endogenous inhibitor of invasive prostate cancer cells.

摘要

内源性大麻素与癌症有关。通过阻断其代谢来增加内源性2-花生四烯酸甘油酯（2-AG）可抑制雄激素非依赖性前列腺癌（PC-3和DU-145）细胞的侵袭。诺拉汀醚（一种稳定的2-AG类似物）和外源性CB1受体激动剂具有类似作用。相反，通过抑制其合成或用拮抗剂阻断其与CB1受体的结合来降低内源性2-AG会增加细胞侵袭。2-AG和诺拉汀醚可降低这些细胞中的蛋白激酶A活性，表明CB1受体与下游效应器偶联。结果表明，通过CB1受体发挥作用的细胞内2-AG是侵袭性前列腺癌细胞的内源性抑制剂。