Apatinib has been shown to apply to a variety of solid tumors, including advanced hepatocellular carcinoma. Preclinical and preliminary clinical results confirmed the synergistic antitumor effects of apatinib in combination with anti-programmed death-1 (PD-1) inhibitors. In this study, we investigated camptothecin (CPT) enhances the anti-tumor effect of low-dose apatinib combined with PD-1 inhibitor on hepatocellular carcinoma. CPT combined with a PD-1 inhibitor enhances the anti-tumor effects of low-dose apatinib in hepatocellular carcinoma which was evaluated in making use of the H22 mouse model (n = 32), which was divided into four groups. Immunohistochemical staining and western blotting were used to detect nuclear factor erythroid 2-related factor 2 (Nrf2) as well as sequestosome 1 (p62), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), PD-1, and programmed cell death ligand 1 (PD-L1). The results showed that the average size of the tumor of the combination group (Group D) was significantly less than that of the apatinib + PD-1 inhibitor group (Group C). The expression levels of Nrf2, p62, VEGFA, VEGFR2, PD-1, and PD-L1 in the apatinib + PD-1 inhibitor group(Group C) were lower than those in the control group (Group A) (P < 0.05). The expression levels of these genes in the apatinib + PD-1 inhibitor group (Group C) were significantly lower in the combination group (Group D) (P < 0.05). There was no obvious difference in body weight and liver and kidney functions between the four groups of mice. In conclusion, CPT improves the anti-tumor effect of low-dose apatinib combined with PD-1 inhibitor on hepatocellular carcinoma

阿帕替尼已被证明适用于多种实体瘤，包括晚期肝细胞癌。临床前和初步临床结果证实了阿帕替尼与抗程序性死亡-1（PD-1）抑制剂联合使用具有协同抗肿瘤作用。在本研究中，我们研究了喜树碱（CPT）增强小剂量阿帕替尼联合PD-1抑制剂对肝细胞癌的抗肿瘤作用。 CPT联合PD-1抑制剂可增强小剂量阿帕替尼对肝细胞癌的抗肿瘤作用，该研究利用H22小鼠模型（n = 32）进行评估，该模型分为四组。采用免疫组化染色和蛋白质印迹法检测核因子红细胞2相关因子2（Nrf2）以及隔离体1（p62）、血管内皮生长因子A（VEGFA）、血管内皮生长因子受体2（VEGFR2）、PD- 1、程序性细胞死亡配体1 (PD-L1)。结果显示，联合组（D组）的肿瘤平均大小明显小于阿帕替尼+PD-1抑制剂组（C组）。阿帕替尼 + PD-1 抑制剂组（C 组）Nrf2、p62、VEGFA、VEGFR2、PD-1、PD-L1 表达水平均低于对照组（A 组）（ P < 0.05  ） 。阿帕替尼 + PD-1 抑制剂组（C 组）这些基因的表达水平显着低于联合组（D 组）（P  < 0.05）。四组小鼠体重及肝肾功能无明显差异。综上所述，CPT提高了小剂量阿帕替尼联合PD-1抑制剂对肝细胞癌的抗肿瘤效果