Department of Clinical and Molecular Biomedicine, University of Catania School of Medicine, Catania, Italy.
Cancer Lett. 2011 Nov 28;310(2):240-9. doi: 10.1016/j.canlet.2011.07.008. Epub 2011 Jul 19.
Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors. While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cells treated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescued from death. WIN induced activation of caspases and phosphorylation of ERK that were attenuated in cultures treated with methylcyclodestrin. Membrane lipid raft complex-mediated antimitogenic effect of WIN in melanoma could represents a potential targets for a melanoma treatment.
报告称，大麻素激动剂 WIN 对表达 CB1 和 CB2 受体 mRNA 和蛋白的人黑色素瘤细胞具有抗增殖作用。WIN 发挥抗有丝分裂作用，而选择性 CB1 或 CB2 激动剂则无法复制这种作用，选择性 CB1 和 CB2 拮抗剂也不能抑制 WIN 诱导的细胞死亡。用甲基环糊精预处理后，用 WIN 处理的细胞从死亡中得到挽救。WIN 诱导了半胱天冬酶的激活和 ERK 的磷酸化，而在用甲基环糊精处理的培养物中，这种激活和磷酸化被减弱。WIN 在黑色素瘤中的膜脂筏复合物介导的抗有丝分裂作用可能是黑色素瘤治疗的一个潜在靶点。
