Cannabidiol (CBD), a primary constituent in hemp and cannabis, exerts broad pharmacological effects against various diseases, including cancer. Additionally, cabozantinib, a potent multi-kinase inhibitor, has been approved for treating patients with advanced hepatocellular carcinoma (HCC). Recently, there has been an increase in research on combination therapy using cabozantinib to improve efficacy and safety when treating patients. Here, we investigated the effect of a combination treatment of cabozantinib and CBD on HCC cells. CBD treatment enhanced the sensitivity of HCC cells to cabozantinib-mediated anti-cancer activity by increasing cytotoxicity and apoptosis. Phospho-kinase array analysis demonstrated that the apoptotic effect of the combination treatment was mainly related to p53 phosphorylation regulated by endoplasmic reticulum (ER) stress when compared to other kinases. The inhibition of p53 expression and ER stress suppressed the apoptotic effect of the combination treatment, revealing no changes in the expression of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-8, or cleaved caspase-9. Notably, the effect of the combination treatment was not associated with cannabinoid receptor 1 (CNR1) and the CNR2 signaling pathways. Our findings suggest that the combination therapy of cabozantinib and CBD provides therapeutic efficacy against HCC.
大麻二酚（CBD）是大麻和工业大麻中的主要成分之一，对多种疾病（包括癌症）具有广泛的药理作用。此外，卡博替尼是一种强效的多激酶抑制剂，已获批准用于治疗晚期肝细胞癌（HCC）患者。近期，关于使用卡博替尼进行联合治疗以提高治疗效果和安全性的研究有所增加。在此，我们研究了卡博替尼与CBD联合治疗对HCC细胞的影响。CBD处理增强了HCC细胞对卡博替尼介导的抗癌活性的敏感性，表现为增加细胞毒性作用和诱导细胞凋亡。磷酸化激酶阵列分析显示，联合治疗的凋亡效应主要与内质网（ER）应激调节的p53磷酸化相关，与其他激酶相比更为显著。抑制p53表达和ER应激可抑制联合治疗的凋亡效应，且Bax、Bcl-2、裂解的caspase-3、裂解的caspase-8或裂解的caspase-9的表达无变化。值得注意的是，联合治疗的效果与大麻素受体1（CNR1）和CNR2信号通路无关。我们的研究结果表明，卡博替尼与CBD的联合疗法对HCC具有治疗效果。
肿瘤(癌症)患者之家