CB1 和 CB2 受体的表达水平决定了它们在诱导星形细胞瘤细胞凋亡中的效力。
The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas.
机构信息
Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.
出版信息
PLoS One. 2010 Jan 14;5(1):e8702. doi: 10.1371/journal.pone.0008702.
BACKGROUND
Cannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB(1) and CB(2) receptors mediate this therapeutic effect is unclear.
PRINCIPAL FINDINGS
We generated astrocytoma subclones that express set levels of CB(1) and CB(2), and found that cannabinoids induce apoptosis only in cells expressing low levels of receptors that couple to ERK1/2. In contrast, cannabinoids do not induce apoptosis in cells expressing high levels of receptors because these now also couple to the prosurvival signal AKT. Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB(1), CB(2) and AKT, but still through a mechanism involving ERK1/2.
SIGNIFICANCE
The high expression level of CB(1) and CB(2) receptors commonly found in malignant astrocytomas precludes the use of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or cannabinoids are applied at concentrations that bypass CB(1) and CB(2) receptors, yet still activate ERK1/2.
背景
大麻素是治疗肿瘤（包括星形细胞瘤）的独特化合物。CB（1）和 CB（2）受体是否介导这种治疗作用尚不清楚。
主要发现
我们生成了表达设定水平 CB（1）和 CB（2）的星形细胞瘤亚克隆，发现大麻素仅在表达与 ERK1/2 偶联的受体水平低的细胞中诱导细胞凋亡。相比之下，大麻素不会诱导表达高受体水平的细胞凋亡，因为这些受体现在也与生存信号 AKT 偶联。值得注意的是，大麻素在高浓度下应用于所有亚克隆，独立于 CB（1）、CB（2）和 AKT，但仍然通过涉及 ERK1/2 的机制。
意义
恶性星形细胞瘤中常见的高表达 CB（1）和 CB（2）受体水平排除了大麻素作为治疗剂的使用，除非 AKT 同时被抑制，或者大麻素以绕过 CB（1）和 CB（2）受体的浓度应用，但仍能激活 ERK1/2。
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