Calycosin is a naturally occurring phytoestrogen, and it has the anti‐nasopharyngeal carcinoma (NPC) action played by calycosin. However, the elaborate mechanisms of calycosin treating NPC remain to be unrevealed. In current report, a promising tool of network pharmacology method was used to uncover the anti‐NPC targets and therapeutic mechanisms played by calycosin. Furthermore, were conducted to validate the bioinformatic findings in human and preclinical studies. As results, the bioinformatic findings showed the core anti‐NPC targets played by calycosin included tumor protein p53 (TP53), mitogen‐activated protein kinase 14 (MAPK14), caspase 8 (CASP8), mitogen‐activated protein kinase 3 (MAPK3), caspase 3 (CASP3), receptor interacting protein kinase 1 (RIPK1), proto‐oncogene c (JUN), and estrogen receptor 1 (ESR1). Concurrently, the top 20 biological processes and top 20 pharmacological pathways of calycosin treating NPC were identified and illustrated. In clinical data, NPC samples showed up‐regulated expression of MAPK14, reduced TP53, and CASP8 expressions in comparison with those in non‐NPC controls. As revealed in experimental data, calycosin‐treated NPC cells resulted in reduced cell survival rate, increased cell apoptosis. In apoptosis‐specific staining, calycosin‐treated NPC cells exhibited elevated apoptotic cell number. Following the immunostaining assays, the results indicated increased TP53‐, CASP8‐positive cells, and reduced MAPK14‐positive cells in calycosin‐treated NPC cells and xenograft tumor sections. Altogether, the bioinformatic findings from network pharmacology reveal all core targets and mechanisms of calycosin treating NPC, and some of bioinformatic findings are identified using human and preclinical experiments. Notably, the screened biotargets may be potentially used to clinically treat NPC.

中文翻译：

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毛蕊花素治疗鼻咽癌的抗癌靶点和机制。

毛蕊花素是一种天然存在的植物雌激素，它具有毛蕊花素所起的抗鼻咽癌 (NPC) 作用。然而，毛蕊花素治疗 NPC 的详细机制仍有待揭示。在当前的报告中，网络药理学方法的一个有前途的工具被用来揭示毛蕊花素的抗 NPC 靶点和治疗机制。此外，还进行了验证人类和临床前研究中的生物信息学发现。结果，生物信息学研究结果表明，毛蕊花素发挥的核心抗 NPC 靶标包括肿瘤蛋白 p53（TP53）、丝裂原活化蛋白激酶 14（MAPK14）、半胱天冬酶 8（CASP8）、丝裂原活化蛋白激酶 3（MAPK3）、 caspase 3 (CASP3)、受体相互作用蛋白激酶 1 (RIPK1)、原癌基因 c (JUN) 和雌激素受体 1 (ESR1)。同时，鉴定并说明了毛蕊花素治疗鼻咽癌的前 20 个生物学过程和前 20 个药理途径。在临床数据中，与非 NPC 对照相比，NPC 样本显示 MAPK14 的表达上调，TP53 和 CASP8 的表达降低。正如实验数据所揭示的那样，毛蕊花素处理的 NPC 细胞导致细胞存活率降低，细胞凋亡增加。在细胞凋亡特异性染色中，毛蕊花素处理的 NPC 细胞表现出升高的凋亡细胞数量。免疫染色分析后，结果表明在毛蕊花素处理的 NPC 细胞和异种移植肿瘤切片中，TP53、CASP8 阳性细胞增加，MAPK14 阳性细胞减少。总之，网络药理学的生物信息学发现揭示了毛蕊花素治疗鼻咽癌的所有核心靶点和机制，一些生物信息学发现是通过人体和临床前实验确定的。值得注意的是，筛选出的生物靶标有可能用于临床治疗 NPC。