Miao Ganggang, Zhang Zhiyu, Wang Meiyan, Gu Xingwei, Xiang Dongxiao, Cao Hongyong
Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of General Surgery, The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang, Zhenjiang, China.
Ann Med Surg (Lond). 2025 Jan 9;87(1):103-112. doi: 10.1097/MS9.0000000000002746. eCollection 2025 Jan.
Berberine (BBR) is an isoquinoline alkaloid extracted from Huang Lian and other herbal medicines. It has been reported to play a crucial role in multiple metabolic diseases and cancers. Programmed cell death-1 (PD-L1) is known as the immune checkpoint; immunotherapy targeting PD1/PD-L1 axis can effectively block its pro-tumor activity. However, the effect of the combined use of BBR and anti-PD-L1 on hepatocellular carcinoma (HCC) has not been reported.
Hep-3B and HCCLM3 cells were chosen as the experimental objects. To determine the potential anti-cancer activity of the combination of BBR and anti-PD-L1, we first treated v cells with BBR. The cell viability of Hep-3B and HCCLM3 with BBR treatment was measured by Cell Count Kit 8 assay. Cytometry by time-of-flight was performed to analyze tumor tissues after treatment with BBR and/or anti-PD-L1. Proliferation-, migration-, and invasion-related markers were measured by western blotting and immunohistochemistry.
The results showed that BBR significantly inhibited the proliferation of Hep-3B and HCCLM3.The combination treatment of BBR and anti-PD-L1 had a prominent inhibitory effect on HCC tumorigenesis. Cytometry by time-of-flight analysis indicated that BBR affects the immune subsets in the tumors. Besides, BBR and anti-PD-L1 inhibited the migration and invasion of HCC by inactivating the phosphorylation of Erk.
Our study proposed that the combination treatment of BBR and anti-PD-L1 markedly inhibited the tumorigenesis of HCC by Erk signaling pathway. We hope our research can provide a new strategy for the potential of BBR as a therapeutic agent in the treatment of HCC.
黄连素（BBR）是一种从黄连等草药中提取的异喹啉生物碱。据报道，它在多种代谢性疾病和癌症中发挥着关键作用。程序性细胞死亡蛋白1（PD-L1）是一种免疫检查点；针对PD1/PD-L1轴的免疫疗法可有效阻断其促肿瘤活性。然而，BBR与抗PD-L1联合使用对肝细胞癌（HCC）的影响尚未见报道。
选用Hep-3B和HCCLM3细胞作为实验对象。为了确定BBR与抗PD-L1联合使用的潜在抗癌活性，我们首先用BBR处理细胞。采用细胞计数试剂盒8法检测BBR处理后Hep-3B和HCCLM3细胞的活力。在用BBR和/或抗PD-L1处理后，通过飞行时间细胞术分析肿瘤组织。通过蛋白质免疫印迹法和免疫组织化学法检测增殖、迁移和侵袭相关标志物。
结果显示，BBR显著抑制Hep-3B和HCCLM3的增殖。BBR与抗PD-L1联合治疗对HCC肿瘤发生具有显著的抑制作用。飞行时间细胞术分析表明，BBR影响肿瘤中的免疫亚群。此外，BBR和抗PD-L1通过使Erk磷酸化失活来抑制HCC的迁移和侵袭。
我们的研究表明，BBR与抗PD-L1联合治疗通过Erk信号通路显著抑制HCC的肿瘤发生。我们希望我们的研究能够为BBR作为治疗HCC的潜在治疗药物提供新的策略。
