Tumor-promoting effects of cannabinoid receptor type 1 in human melanoma cells

被引:25
作者
Carpi, Sara [1 ]
Fogli, Stefano [1 ]
Polini, Beatrice [1 ]
Montagnani, Valentina [2 ]
Podesta, Adriano [3 ]
Breschi, Maria Cristina [1 ]
Romanini, Antonella [4 ]
Stecca, Barbara [2 ]
Nieri, Paola [1 ]
机构
[1] Univ Pisa, Dept Pharm, Via Bonanno 6, I-56126 Pisa, Italy
[2] Ist Toscano Tumori CRL IFF, Core Res Lab, Tumor Cell Biol Lab, Florence, Italy
[3] Univ Pisa, Vet Sci, I-56100 Pisa, Italy
[4] Univ Hosp Pisa, Pisa, Italy
关键词
Melanoma; Cannabinoid receptor type 1; Tumorigenic role; CYCLE PROGRESSION; CB1; RECEPTORS; MAP-KINASE; ANANDAMIDE; ENDOCANNABINOIDS; SYSTEM; PROLIFERATION; ACTIVATION; LIVER;
D O I
10.1016/j.tiv.2017.01.018
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The role of endocannabinoid system in melanoma development and progreSsion is actually not fully understood. This study was aimed at clarifying whether cannabinoid-type 1 (01) receptor may function as tumor-promoting or-suppressing signal in human cutaneous melanoma. CB1 receptor expression was measured in human melanoma cell lines by real-time PCR. A genetic deletion of CB1 receptors in selected melanoma cells was carried out by using three different short hairpin RNAs (shRNAs). Performance of target gene silencing was verified by realtime PCR and Western blot. The effects of CB1 receptor silencing on cell growth, clonogenicity, migration capability, cell cycle progression, and activation of mitogenic signals Was tested. Lentiviral shRNAs vectors targeting different regions of the human CB1 gene led to a significant reduction in CBI receptor mRNA and a near complete loss of CB1 receptor protein, compared to control vector (LV-c). The number of viable cells, the colony-forming ability and cell migration were significantly reduced in cells transduced with CB1 lentiviral shRNAs compared to LV-c. Cell cycle analyses showed arrest at Gl/S phase. p-Akt and p-ERR expression were decreased in transduced versus control cells. Findings of this study suggest that CB1 receptor might function as tumor-promoting signal in human cutaneous melanoma. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:272 / 279
页数:8
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