Fang Yi, Yang Chi, Lu Yao, Wei Lihui, Zhao Jinyan, Lu Lisha, Lin Jiumao
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
Evid Based Complement Alternat Med. 2022 Mar 4;2022:7242640. doi: 10.1155/2022/7242640. eCollection 2022.
Qingjie Fuzheng granules (QFG) exert an anticancer effect against colorectal cancers (CRC). However, the pharmacological molecular mechanisms are still unclear. This study was aimed to establish a simple method to predict targets of QFG against CRC by the network pharmacology strategy. 461 compounds and 1559 targets in QFG were enriched by BATMAN-TCM. 21 of the common targets were obtained by the groups of "Jun," "Chen," "Zuo," and "Shi" medicine in QFG. The enrichment analyses of GO functional terms, KEGG pathway, and OMIM/TTD diseases displayed the targets in the different and complementary effects of four functional medicines in QFG. Then, 613 differential targets for QFG in CRC were identified. GO functional terms and KEGG pathway analyses showed that QFG regulated the inflammatory function and lipid metabolic process. There were also targets that played a role in the binding to the receptors in membranes, in the activation of the transportation signal, and provided pain relief by regulation of the neural related pathways. Next, the protein-protein interaction network was analyzed, and the levels of the predicted targets in CRC primary tumor were explored, and 7 candidate targets of QFG against CRC were obtained. Furthermore, with real-time PCR and enzyme-linked immunosorbent assay (ELISA) analysis, downregulation of dopamine D2 receptor (DRD2) and interleukin-6 (IL-6), and upregulation of interleukin-10 (IL-10) were identified following the treatment of QFG. At last, the survival and prognosis of the potential targets of QFG in CRC patients were analyzed by GenomicScape, and IL-6 was suggested to be an index for the regulation of QFG in CRC. These results might elucidate the possible antitumor mechanism of QFG and highlight the candidate therapeutic targets and the application direction in clinical treatment for QFG.
清解扶正颗粒（QFG）对结直肠癌（CRC）具有抗癌作用。然而，其药理分子机制仍不清楚。本研究旨在通过网络药理学策略建立一种简单的方法来预测QFG抗CRC的靶点。通过BATMAN-TCM富集了QFG中的461种化合物和1559个靶点。通过QFG中“君”“臣”“佐”“使”药组获得了21个共同靶点。GO功能术语、KEGG通路和OMIM/TTD疾病的富集分析显示了QFG中四种功能药物的不同和互补作用的靶点。然后，确定了QFG在CRC中的613个差异靶点。GO功能术语和KEGG通路分析表明，QFG调节炎症功能和脂质代谢过程。也有一些靶点在与膜受体结合、激活转运信号以及通过调节神经相关通路提供疼痛缓解方面发挥作用。接下来，分析了蛋白质-蛋白质相互作用网络，探索了CRC原发性肿瘤中预测靶点的水平，获得了QFG抗CRC的7个候选靶点。此外，通过实时PCR和酶联免疫吸附测定（ELISA）分析，发现QFG处理后多巴胺D2受体（DRD2）和白细胞介素-6（IL-6）下调，白细胞介素-10（IL-10）上调。最后，通过GenomicScape分析了QFG在CRC患者中潜在靶点的生存和预后，提示IL-6是QFG在CRC中调节的一个指标。这些结果可能阐明了QFG可能的抗肿瘤机制，并突出了候选治疗靶点以及QFG在临床治疗中的应用方向。
