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植物大麻素在间皮瘤临床前模型中的抗癌特性研究。

An Examination of the Anti-Cancer Properties of Plant Cannabinoids in Preclinical Models of Mesothelioma.

作者信息

Colvin Emily K, Hudson Amanda L, Anderson Lyndsey L, Kumar Ramyashree Prasanna, McGregor Iain S, Howell Viive M, Arnold Jonathon C

机构信息

Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, St Leonards 2065, Australia.

School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia.

出版信息

Cancers (Basel). 2022 Aug 5;14(15):3813. doi: 10.3390/cancers14153813.

DOI:10.3390/cancers14153813
PMID:35954477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9367527/
Abstract

Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in mesothelioma cell lines. A panel of 13 phytocannabinoids inhibited growth of human (MSTO and H2452) and rat (II-45) mesothelioma cells in vitro, and cannabidiol (CBD) and cannabigerol (CBG) were the most potent compounds. Treatment with CBD or CBG resulted in G0/G1 arrest, delayed entry into S phase and induced apoptosis. CBD and CBG also significantly reduced mesothelioma cell migration and invasion. These effects were supported by changes in the expression of genes associated with the cell cycle, proliferation, and cell movement following CBD or CBG treatment. Gene expression levels of , , and also increased with CBD or CBG treatment. However, treatment with CBD or CBG in a syngeneic orthotopic rat mesothelioma model was unable to increase survival. Our data show that cannabinoids have anti-cancer effects on mesothelioma cells in vitro and alternatives of drug delivery may be needed to enhance their effects in vivo.

摘要

间皮瘤是一种侵袭性癌症，治疗选择有限且预后较差。植物大麻素在多种癌症中具有抗肿瘤和姑息治疗特性，然而它们在间皮瘤中的作用尚不清楚。我们研究了几种植物大麻素在间皮瘤细胞系中的抗癌作用及潜在作用机制。一组13种植物大麻素在体外抑制了人（MSTO和H2452）和大鼠（II-45）间皮瘤细胞的生长，大麻二酚（CBD）和大麻萜酚（CBG）是最有效的化合物。用CBD或CBG处理导致G0/G1期阻滞，延迟进入S期并诱导凋亡。CBD和CBG还显著降低了间皮瘤细胞的迁移和侵袭。这些作用得到了CBD或CBG处理后与细胞周期、增殖和细胞运动相关基因表达变化的支持。 、 和 的基因表达水平也随着CBD或CBG处理而增加。然而，在同基因原位大鼠间皮瘤模型中用CBD或CBG处理并不能提高生存率。我们的数据表明，大麻素在体外对间皮瘤细胞具有抗癌作用，可能需要替代的给药方式来增强它们在体内的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/15e0cd1849be/cancers-14-03813-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/20de80d72c59/cancers-14-03813-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/8f7ad4967ecd/cancers-14-03813-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/8e2ef08c0e24/cancers-14-03813-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/3aef7fafcf06/cancers-14-03813-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/95fa0a4f5739/cancers-14-03813-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/6697ead43314/cancers-14-03813-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/15e0cd1849be/cancers-14-03813-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/20de80d72c59/cancers-14-03813-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/8f7ad4967ecd/cancers-14-03813-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/8e2ef08c0e24/cancers-14-03813-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/3aef7fafcf06/cancers-14-03813-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/95fa0a4f5739/cancers-14-03813-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/6697ead43314/cancers-14-03813-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/9367527/15e0cd1849be/cancers-14-03813-g007.jpg

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