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EC/EV系统在人骨肉瘤中的抗增殖、促凋亡和抗侵袭作用

Anti-proliferative, pro-apoptotic and anti-invasive effect of EC/EV system in human osteosarcoma.

作者信息

Punzo Francesca, Tortora Chiara, Di Pinto Daniela, Manzo Iolanda, Bellini Giulia, Casale Fiorina, Rossi Francesca

机构信息

Department of Women, Child and General and Specialist Surgery, Second University of Naples, 80138 Naples, Italy.

Department of Experimental Medicine, Division of Pharmacology "Leonardo Donatelli", The Second University of Naples, 80138 Naples, Italy.

出版信息

Oncotarget. 2017 Apr 13;8(33):54459-54471. doi: 10.18632/oncotarget.17089. eCollection 2017 Aug 15.

DOI:10.18632/oncotarget.17089
PMID:28903355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5589594/
Abstract

Osteosarcoma is the most common and aggressive bone tumor in children. The Endocannabinoid/Endovanilloid system has been proposed as anticancer target in tumor of different origins. This system is composed of two receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel and their ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells. We investigated the effects of JWH-133 (CB2 agonist) and RTX (TRPV1 agonist) in six human Osteosarcoma cell lines: MG-63, U-2OS, MNNG/HOS, Saos-2, KHOS/NP, Hs888Lu, by Apoptosis and Migration-Assay. We also compared the effects of these compounds on Caspase-3, AKT, MMP-2 and Notch-1 regulation by Q-PCR and Western Blotting. We observed an anti-proliferative, pro-apoptotic, anti-invasive effect. Our results show that both CB2 stimulation and TRPV1 activation, in different Osteosarcoma cell lines, can act on the same pathways to obtain the same effect, indicating the Endocannabinoid/Endovanilloid system as a new therapeutic target in Osteosarcoma.

摘要

骨肉瘤是儿童中最常见且侵袭性最强的骨肿瘤。内源性大麻素/内源性香草素系统已被提议作为不同起源肿瘤的抗癌靶点。该系统由两种受体（CB1和CB2）、瞬时电位香草酸受体1（TRPV1）通道及其配体和酶组成。CB1主要在中枢神经系统中表达，而CB2主要在免疫细胞和外周细胞上表达。我们通过凋亡和迁移试验研究了JWH-133（CB2激动剂）和RTX（TRPV1激动剂）对六种人骨肉瘤细胞系：MG-63、U-2OS、MNNG/HOS、Saos-2、KHOS/NP、Hs888Lu的影响。我们还通过定量聚合酶链反应（Q-PCR）和蛋白质免疫印迹法比较了这些化合物对Caspase-3、AKT、基质金属蛋白酶-2（MMP-2）和Notch-1调节的影响。我们观察到了抗增殖、促凋亡和抗侵袭作用。我们的结果表明，在不同的骨肉瘤细胞系中，CB2刺激和TRPV1激活均可作用于相同的信号通路以获得相同的效果，这表明内源性大麻素/内源性香草素系统是骨肉瘤的一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/0e8fbd911785/oncotarget-08-54459-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/3177ee51ef1d/oncotarget-08-54459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/0c61137a44f8/oncotarget-08-54459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/ed2a6a455e2c/oncotarget-08-54459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/6e6a67f6ea4d/oncotarget-08-54459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/70bcda7bb6b0/oncotarget-08-54459-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/f839693dea44/oncotarget-08-54459-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/cd2d650b3aae/oncotarget-08-54459-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/0e8fbd911785/oncotarget-08-54459-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/3177ee51ef1d/oncotarget-08-54459-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/0c61137a44f8/oncotarget-08-54459-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/ed2a6a455e2c/oncotarget-08-54459-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/6e6a67f6ea4d/oncotarget-08-54459-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/70bcda7bb6b0/oncotarget-08-54459-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/f839693dea44/oncotarget-08-54459-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/cd2d650b3aae/oncotarget-08-54459-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e1/5589594/0e8fbd911785/oncotarget-08-54459-g008.jpg

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