Department of Otolaryngology Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
Department of Oncology, Guigang City Peoples' Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, Guangxi, China.
Biofactors. 2020 Jul;46(4):675-684. doi: 10.1002/biof.1639. Epub 2020 May 24.
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.
毛蕊异黄酮是一种天然存在的植物雌激素，具有毛蕊异黄酮发挥的抗鼻咽癌（NPC）作用。然而，毛蕊异黄酮治疗 NPC 的精细机制仍有待揭示。在目前的报告中，使用一种有前途的网络药理学方法工具来揭示毛蕊异黄酮的抗 NPC 靶点和治疗机制。此外，在人体和临床前研究中进行了验证生物信息学发现。结果表明，生物信息学发现毛蕊异黄酮发挥的核心抗 NPC 靶点包括肿瘤蛋白 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）、半胱天冬酶 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，确定并说明了毛蕊异黄酮治疗 NPC 的前 20 个生物学过程和前 20 个药理学途径。在临床数据中，与非 NPC 对照相比，NPC 样本显示 MAPK14 表达上调，TP53 和 CASP8 表达下调。如实验数据所示，毛蕊异黄酮处理的 NPC 细胞导致细胞存活率降低，细胞凋亡增加。在凋亡特异性染色中，毛蕊异黄酮处理的 NPC 细胞显示出凋亡细胞数量增加。免疫染色测定后，结果表明毛蕊异黄酮处理的 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异黄酮治疗 NPC 的所有核心靶点和机制，其中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，筛选出的生物靶标可能可用于临床治疗 NPC。
