Flygare Jenny, Gustafsson Kristin, Kimby Eva, Christensson Birger, Sander Birgitta
Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Karolinska University Hospital Huddinge, F-46, SE-141 86 Stockholm, Sweden.
FEBS Lett. 2005 Dec 19;579(30):6885-9. doi: 10.1016/j.febslet.2005.11.020.
We have earlier reported overexpression of the central and peripheral cannabinoid receptors CB1 and CB2 in mantle cell lymphoma (MCL), a B cell non-Hodgkin lymphoma. In this study, treatment with cannabinoid receptor ligands caused a decrease in viability of MCL cells, while control cells lacking CB1 were not affected. Interestingly, equipotent doses of the CB1 antagonist SR141716A and the CB1/CB2 agonist anandamide inflicted additive negative effects on viability. Moreover, treatment with the CB1/CB2 agonist Win-55,212-2 caused a decrease in long-term growth of MCL cells in culture. Induction of apoptosis, as measured by FACS/Annexin V-FITC, contributed to the growth suppressive effect of Win-55,212-2. Our data suggest that cannabinoid receptors may be considered as potential therapeutic targets in MCL.
我们之前报道过，中枢和外周大麻素受体CB1和CB2在套细胞淋巴瘤（MCL，一种B细胞非霍奇金淋巴瘤）中过表达。在本研究中，用大麻素受体配体处理导致MCL细胞活力下降，而缺乏CB1的对照细胞则未受影响。有趣的是，等剂量的CB1拮抗剂SR141716A和CB1/CB2激动剂花生四烯乙醇胺对细胞活力产生了累加的负面影响。此外，用CB1/CB2激动剂Win-55,212-2处理导致培养的MCL细胞长期生长减少。通过流式细胞术/膜联蛋白V-异硫氰酸荧光素检测到的凋亡诱导作用，促成了Win-55,212-2的生长抑制效应。我们的数据表明，大麻素受体可被视为MCL潜在的治疗靶点。
