Zhu Jinglin, Huang Ruifei, Yang Ruijie, Xiao Yue, Yan Jiangna, Zheng Chunli, Xiao Wei, Huang Chao, Wang Yonghua
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, China.
State Key Laboratory of New-Tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Parmaceutical, Co., Ltd, Lianyungang, China.
Cancer Cell Int. 2021 Oct 12;21(1):529. doi: 10.1186/s12935-021-02223-0.
Targeting tumor microenvironment (TME) may provide therapeutic activity and selectivity in treating cancers. Therefore, an improved understanding of the mechanism by which drug targeting TME would enable more informed and effective treatment measures. Glycyrrhiza uralensis Fisch (GUF, licorice), a widely used herb medicine, has shown promising immunomodulatory activity and anti-tumor activity. However, the molecular mechanism of this biological activity has not been fully elaborated.
Here, potential active compounds and specific targets of licorice that trigger the antitumor immunity were predicted with a systems pharmacology strategy. Flow cytometry technique was used to detect cell cycle profile and CD8 T cell infiltration of licorice treatment. And anti-tumor activity of licorice was evaluated in the C57BL/6 mice.
We reported the G0/G1 growth phase cycle arrest of tumor cells induced by licorice is related to the down-regulation of CDK4-Cyclin D1 complex, which subsequently led to an increased protein abundance of PD-L1. Further, in vivo studies demonstrated that mitigating the outgrowth of NSCLC tumor induced by licorice was reliant on increased antigen presentation and improved CD8 T cell infiltration.
Briefly, our findings improved the understanding of the anti-tumor effects of licorice with the systems pharmacology strategy, thereby promoting the development of natural products in prevention or treatment of cancers.
靶向肿瘤微环境（TME）可能为癌症治疗提供治疗活性和选择性。因此，更好地理解药物靶向TME的机制将有助于采取更明智和有效的治疗措施。甘草是一种广泛使用的草药，已显示出有前景的免疫调节活性和抗肿瘤活性。然而，这种生物活性的分子机制尚未完全阐明。
在此，采用系统药理学策略预测甘草触发抗肿瘤免疫的潜在活性化合物和特定靶点。使用流式细胞术检测甘草处理后的细胞周期分布和CD8 T细胞浸润情况。并在C57BL/6小鼠中评估甘草的抗肿瘤活性。
我们报道甘草诱导的肿瘤细胞G0/G1生长阶段周期停滞与CDK4-Cyclin D1复合物的下调有关，这随后导致PD-L1蛋白丰度增加。此外，体内研究表明，甘草减轻非小细胞肺癌肿瘤生长依赖于抗原呈递增加和CD8 T细胞浸润改善。
简而言之，我们的研究结果通过系统药理学策略增进了对甘草抗肿瘤作用的理解，从而促进天然产物在癌症预防或治疗中的开发。
