Cannabidiol Treatment Results in a Common Gene Expression Response Across Aggressive Cancer Cells from Various Origins
Cannabidiol Treatment Results in a Common Gene Expression Response Across Aggressive Cancer Cells from Various Origins
复制标题
大麻二酚治疗导致来自不同来源的侵袭性癌细胞的共同基因表达反应
DOI：
10.1089/can.2019.0081
复制
发表时间：
2021-04-01
影响因子：
3.8
通讯作者：
McAllister, Sean D.
中科院分区：
文献类型：
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作者：
Desprez, Pierre-Yves;Murase, Ryuichi;McAllister, Sean D.
背景资料：我们以前报道过大麻二酚（CBD），一种低毒性的大麻素，下调癌细胞中DNA结合1（ID1）的促转移基因抑制剂的表达，导致体内肿瘤进展的抑制。虽然CBD被广泛使用，包括在癌症患者的自我药物治疗中，并且基于CBD的疗法正在进行癌症治疗的临床评估，但其作用机制仍然知之甚少。在这项研究中，使用微阵列分析和蛋白质印迹分析进行验证，我们试图在各种侵袭性癌细胞系中鉴定CBD调控的全谱基因，包括乳腺癌，脑癌，结果：证实ID1是CBD下调的主要靶点，CBD抑制FOXM1，（叉头框M1），一种参与细胞增殖的转录激活因子，同时上调GDF 15（生长分化因子15），一种与组织分化相关的细胞因子。我们的研究结果表明，通过调节共享的关键癌症驱动基因的表达，CBD可以代表一种有前途的无毒治疗方法，用于治疗各种来源的肿瘤。
Background: We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, downregulated the expression of the prometastatic gene inhibitor of DNA binding 1 (ID1) in cancer cells, leading to inhibition of tumor progression in vivo. While CBD is broadly used, including in the self-medication of cancer patients, and CBD-based therapies are undergoing clinical evaluation for cancer treatment, its mechanisms of action are still poorly understood.Methods: In this study, using microarray analysis and Western blot analysis for validation, we attempted to identify the full spectrum of genes regulated by CBD across various aggressive cancer cell lines, including the breast, brain, head and neck, and prostate.Results: We confirmed that ID1 was a major target downregulated by CBD and also discovered that CBD inhibited FOXM1 (Forkhead box M1), a transcriptional activator involved in cell proliferation, while simultaneously upregulating GDF15 (growth differentiation factor 15), a cytokine associated with tissue differentiation.Conclusion: Our results suggest that, by modulating expression of shared key cancer-driving genes, CBD could represent a promising nontoxic therapeutic for treating tumors of various origins.