Recent evidences have suggested that genistein, a beneficial isoflavonoid, exerts marked anti‐proliferative action on colorectal cancer (CRC) cells. However, the exact molecular mechanisms behind anti‐CRC effect of genistein have not been elucidated. In current report, a systemic pharmacology analysis was used to disclose the anti‐CRC mechanism of genistein prior to performing experimentative certification. As shown in network pharmacology findings, a total of 189 common targets and 9 hard‐core targets of genistein‐anti‐CRC were collected and identified. And the detailed anti‐CRC functions and pathways mediated by genistein were uncovered. In further certification, human CRC samples resulted in elevated protein and mRNA expressions of myeloid leukemia cell differentiation protein (MCL1), beta amyloid A4 protein (APP), and vascular endothelial growth factor receptor 2 (KDR). In animal experiment, genistein‐treated tumor‐transplanted nude mice exhibited reduced tumor growth, accompanied with dose‐dependent down‐regulations of MCL1, APP, and KDR proteins and mRNAs. Taken together, the integrated bioinformatic and experimental findings uncover the anti‐CRC mechanisms and targets mediated by genistein. Significantly, parts of hard‐core biotargets were experimentally verified before clinical application, including MCL1, APP, and KDR.

中文翻译：

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染料木素介导的抗结直肠癌的系统和实验研究。

最近的证据表明，染料木黄酮是一种有益的异黄酮，对结直肠癌 (CRC) 细胞具有显着的抗增殖作用。然而，染料木黄酮抗结直肠癌作用背后的确切分子机制尚未阐明。在当前的报告中，在进行实验认证之前，系统药理学分析被用来揭示染料木黄酮的抗 CRC 机制。如网络药理学研究结果所示，共收集和鉴定了染料木黄酮-抗CRC的189个常见靶点和9个核心靶点。并且揭示了由染料木黄酮介导的详细的抗CRC功能和途径。在进一步证明中，人类 CRC 样本导致髓系白血病细胞分化蛋白 (MCL1)、β 淀粉样蛋白 A4 蛋白 (APP)、和血管内皮生长因子受体 2 (KDR)。在动物实验中，金雀异黄素处理的肿瘤移植裸鼠表现出肿瘤生长减少，伴随着剂量依赖性的 MCL1、APP 和 KDR 蛋白和 mRNA 的下调。总之，综合的生物信息学和实验结果揭示了染料木素介导的抗 CRC 机制和靶点。重要的是，部分核心生物靶点在临床应用前经过实验验证，包括 MCL1、APP 和 KDR。综合生物信息学和实验结果揭示了染料木素介导的抗 CRC 机制和靶点。重要的是，部分核心生物靶点在临床应用前经过实验验证，包括 MCL1、APP 和 KDR。综合生物信息学和实验结果揭示了染料木素介导的抗 CRC 机制和靶点。重要的是，部分核心生物靶点在临床应用前经过实验验证，包括 MCL1、APP 和 KDR。