Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB and cell growth in U87MG human malignant glioma cells
Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB and cell growth in U87MG human malignant glioma cells
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DOI：
10.3892/or.2012.1937
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发表时间：
2012-10-01
期刊：
影响因子：
4.2
通讯作者：
Ohno-Shosaku, Takako
中科院分区：
文献类型：
--
作者：
Echigo, Ryosuke;Sugimoto, Naotoshi;Ohno-Shosaku, Takako
核因子(NF)- κ B是参与炎症反应的关键转录因子，其激活可加重肿瘤。肽聚糖（PGN）是革兰氏阳性细菌的主要细胞壁成分，可刺激toll样受体2 （TLR-2）并激活多种炎症通路，包括nf - κ b。然而，这些行为背后的机制在很大程度上是未知的。本研究旨在探讨大麻素是否能通过大麻素受体抑制pgnn诱导的NF-kappa B的活化和U87MG人恶性胶质瘤细胞的生长。PGN处理诱导nf - κ B磷酸化和细胞增殖呈浓度依赖性。主要的内源性大麻素，2-花生四烯醇甘油，阻止了pgnn诱导的NF-kappa B的磷酸化，这被CBI大麻素受体拮抗剂AM281逆转。合成大麻素WIN55,212-2可以消除pgnn激活的细胞生长，这种作用被AM281逆转。通过逆转录介导的聚合酶链反应实验证实了这些细胞中CBI比CB2受体更优先表达，并观察到win55,212 -2诱导的形态学变化被AM281完全逆转，而CB2拮抗剂AM630则不能。我们发现大麻素通过CB1受体抑制神经胶质瘤细胞中的NF-kappa B炎症途径和细胞生长，为靶向大麻素受体治疗炎症依赖性肿瘤进展的治疗潜力提供了证据。
Nuclear factor (NF)-kappa B is the key transcription factor involved in the inflammatory responses, and its activation aggravates tumors. Peptidoglycan (PGN), a main cell wall component of Gram-positive bacteria, stimulates Toll-like receptor 2 (TLR-2) and activates a number of inflammatory pathways, including NF-kappa B. Cannabinoids have been reported to exert anti-inflammatory and antitumor effects. The mechanisms underlying these actions, however, are largely unknown. The purpose of this study was to investigate whether cannabinoids can suppress the PGN-induced activation of NF-kappa B and cell growth via cannabinoid receptors in U87MG human malignant glioma cells. PGN treatment induced the phosphorylation of NF-kappa B and cell proliferation in a concentration-dependent manner. The main endocannabinoid, 2-arachidonoylglycerol, prevented the PGN-induced phosphorylation of NF-kappa B, which was reversed by the CBI cannabinoid receptor antagonist, AM281. The synthetic cannabinoid, WIN55,212-2, abolished the PGN-activated cell growth, and this effect was reversed by AM281. The preferential expression of CBI rather than CB2 receptors in these cells was confirmed by reverse transcription-mediated polymerase chain reaction experiments and the observation that the WIN55,212-2-induced morphological changes were completely reversed by AM281 but not by the CB2 antagonist, AM630. Our finding that cannabinoids suppress the NF-kappa B inflammatory pathway and cell growth via CB1 receptors in glioma cells provides evidence for the therapeutic potential of targeting cannabinoid receptors for the treatment of inflammation-dependent tumor progression.