Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
Fujian Key Laboratory of Translational Cancer Medicine, Fujian, Fuzhou, China.
J Biochem Mol Toxicol. 2023 Sep;37(9):e23401. doi: 10.1002/jbt.23401. Epub 2023 Jun 20.
Immune checkpoint therapy is an emerging frontier in cancer therapy. With the aim to develop an efficient herb derived compound to facilitate immune checkpoint therapy, here we investigate if a herb-derived compound, Bakuchiol (BAK), can be used to treat lung cancer and elucidate if BAK could serve as a PD-L1 regulator. To this end, a murine lung cancer model was established by subcutaneously inoculating murine Lewis lung carcinoma (LLC) cells. BAK of 5 to 40 mg/kg was used for treatment in vivo for 15 days. On Day 15, the population of CD4+ and CD8+ T cells, Treg cells. BAK could effectively inhibit tumor growth by starting treatment either on Day 0 or 6 after tumor inoculation at doses of 5-40 mg/kg. BAK treatment increased the population of cytotoxic immune cells (i.e., CD8+ T cells, and M1 macrophages), meanwhile decreasing pro-tumor immune cells (i.e., CD3+ T cells, Treg cells, and M2 macrophages). Anti-inflammatory cytokines, including IL1β, IL2, IFNγ, TNF-α, IL4 and IL10 were upregulated by BAK. PD-L1 expression in the tumor was also lowered by BAK. AKT and STAT3 signaling were inhibited by BAK. BAK is an efficient agent in reducing LLC tumor growth. These data support the potential of BAK as a new drug for treating lung cancer by serving as a PD-L1 inhibitor that suppresses the activation of AKT and STAT3.
免疫检查点疗法是癌症治疗的一个新兴领域。本研究旨在开发一种有效的植物衍生化合物，以促进免疫检查点疗法，在此我们研究一种植物衍生化合物巴卡丁 III（BAK）是否可用于治疗肺癌，并阐明 BAK 是否可作为 PD-L1 调节剂。为此，通过皮下接种小鼠 Lewis 肺癌（LLC）细胞建立了小鼠肺癌模型。在体内用 5 至 40mg/kg 的 BAK 治疗 15 天。第 15 天，检测 CD4+和 CD8+T 细胞、Treg 细胞的群体。BAK 能够通过在肿瘤接种后第 0 天或第 6 天开始治疗，在 5-40mg/kg 的剂量下有效抑制肿瘤生长。BAK 治疗增加了细胞毒性免疫细胞（即 CD8+T 细胞和 M1 巨噬细胞）的群体，同时减少了促肿瘤免疫细胞（即 CD3+T 细胞、Treg 细胞和 M2 巨噬细胞）。BAK 上调了抗炎细胞因子，包括 IL1β、IL2、IFNγ、TNF-α、IL4 和 IL10。BAK 还降低了肿瘤中的 PD-L1 表达。BAK 抑制了 AKT 和 STAT3 信号通路。BAK 是一种有效降低 LLC 肿瘤生长的药物。这些数据支持 BAK 作为一种新的治疗肺癌的药物的潜力，其作为 PD-L1 抑制剂可抑制 AKT 和 STAT3 的激活。
