Abstract：
Cannabidiol (CBD) has antioxidant and anti-inflammatory activities. However, the anti-tumor effect of CBD on hepatocellular carcinoma (HCC) remains unclear. Here, we investigated whether CBD displays anti-tumorigenic effects in HCC cells and whether it could reduce tumorigenesis and metastases in vivo. First, this study treated HCC cells with different concentrations of CBD, followed by analyzing the changes in the proliferative, apoptotic, migratory and invasive abilities. The effects of CBD on the growth and metastasis of HCC cells in vivo were verified by tumorigenesis and metastasis assays. Subsequently, the target genes of CBD were predicted through the SwissTarget website and the genes differentially expressed in cells after CBD treatment were analyzed by microarray for intersection. The enrichment of the pathways after CBD treatment was analyzed by KEGG enrichment analysis, followed by western blot validation. Finally, rescue assays were used to validate the functions of genes as well as pathways in the growth and metastasis of HCC cells. A significant weakening of the ability of HCC cells to grow and metastasize in vitro and in vivo was observed upon CBD treatment. Mechanistically, CBD reduced GRP55 expression in HCC cells, along with increased TP53 expression and blocked MAPK signaling activation. In CBD-treated cells, the anti-tumor of HCC cells was restored after overexpression of GRP55 or deletion of TP53. CBD inhibits the MAPK signaling activation and increases the TP53 expression by downregulating GRP55 in HCC cells, thereby suppressing the growth and metastasis of HCC cells.
摘要：
大麻二酚（CBD）具有抗氧化和抗炎活性。然而,CBD对肝细胞癌（HCC）的抗肿瘤作用尚不清楚。这里,我们研究了CBD是否在HCC细胞中显示出抗肿瘤作用，以及它是否可以减少体内肿瘤发生和转移。首先,本研究用不同浓度的CBD处理HCC细胞，然后分析增殖的变化，凋亡，迁移和侵入能力。通过肿瘤发生和转移试验验证了CBD对体内HCC细胞生长和转移的影响。随后，通过SwissTarget网站预测CBD的靶基因，并通过微阵列分析CBD处理后细胞中差异表达的基因的交叉。通过KEGG富集分析分析CBD处理后途径的富集，其次是westernblot验证。最后,使用拯救试验来验证基因的功能以及在HCC细胞生长和转移中的途径。在CBD处理后，观察到HCC细胞在体外和体内生长和转移的能力显着减弱。机械上,CBD降低GRP55在HCC细胞中的表达，随着TP53表达的增加和MAPK信号激活的阻断。在CBD处理的细胞中，GRP55过表达或TP53缺失后，HCC细胞的抗肿瘤能力得以恢复。CBD抑制MAPK信号激活，并通过下调GRP55在HCC细胞中增加TP53表达，从而抑制HCC细胞的生长和转移。
