This article was designed by using a network pharmacological approach to reveal the therapeutic targets and molecular mechanisms of oxyresveratrol (Oxyres) treating colorectal cancer (CRC). Furthermore, several bioinformatic findings would be validated. Pathogenetic targets of CRC and pharmacological targets of Oxyres were identified by web‐available databases. All identifiable biotargets were collected for functional enrichment analyses to reveal the biological processes and signaling pathways of Oxyres treating CRC. In addition, human CRC, non‐CRC samples, and cell line study were used to validate the predictive biotargets of Oxyres treating CRC. In network pharmacological analyses, top therapeutic targets of mitogen‐activated protein kinase 1 (MAPK1), insulin growth factor 1 (IGF1), hematopoietic prostaglandin D synthase (HPGDS), GTPase HRas (HRAS), and cytochrome P450 2C9 (CYP2C9) in Oxyres treating CRC were identified, respectively. As shown in functional analysis, biological processes of Oxyres treating CRC were mainly involved in modulating cell communication, signal transduction, apoptosis, cell motility, cell proliferation, and lipid metabolism. Furthermore, top 10 signaling pathways of Oxyres treating CRC were identified, respectively. In human study, CRC samples resulted in increased neoplastic expressions of Ki‐67, MAPK1, IGF1, characterized with clinical imaging inspection, pathological diagnosis, and altered blood lipids in these CRC cases. In cell culture study, Oxyres‐dosed CRC cells exhibited reduced cell proliferation, promoted cellular apoptosis. Furthermore, significantly decreased proteins of intracellular Ki‐67, MAPK1, and IGF1 were observed in Oxyres‐dosed cells when compared to those in controls. Collectively, anti‐CRC pharmacological activity of Oxyres may be mainly associated with induction of apoptosis and suppression of cell proliferation as revealed in bioinformatic findings. In addition, all core biotargets and molecular mechanisms of Oxyres treating CRC are unveiled respectively. Interestingly, the identifiable MAPK1, IGF1 biotargets may be potential molecules for treating and screening CRC.

中文翻译：

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氧白藜芦醇治疗结直肠癌的药理生物靶点和分子机制：网络和实验分析。

本文通过网络药理学方法设计，揭示了氧白藜芦醇（Oxyres）治疗结直肠癌（CRC）的治疗靶点和分子机制。此外，一些生物信息学的发现将得到验证。可通过网络上的数据库确定CRC的致病靶标和Oxyres的药理学靶标。收集所有可识别的生物靶标进行功能富集分析，以揭示Oxyres治疗CRC的生物学过程和信号传导途径。此外，人类CRC，非CRC样本和细胞系研究被用于验证Oxyres治疗CRC的预测生物靶标。在网络药理分析中，有丝分裂原激活的蛋白激酶1（MAPK1），胰岛素生长因子1（IGF1），造血前列腺素D合酶（HPGDS），在治疗CRC的Oxyres中分别鉴定了GTPase HRas（HRAS）和细胞色素P450 2C9（CYP2C9）。如功能分析所示，Oxyres治疗CRC的生物学过程主要涉及调节细胞通讯，信号转导，凋亡，细胞运动，细胞增殖和脂质代谢。此外，分别确定了Oxyres治疗CRC的前10条信号通路。在人体研究中，CRC样品导致Ki‐67，MAPK1，IGF1的肿瘤表达增加，其特征在于临床影像学检查，病理学诊断和这些CRC病例中血脂的改变。在细胞培养研究中，以Oxyres给药的CRC细胞显示出减少的细胞增殖，促进了细胞凋亡。此外，细胞内Ki‐67，MAPK1，与对照相比，在Oxyres剂量的细胞中观察到了IGF1和IGF1。总的来说，Oxyres的抗CRC药理活性可能主要与诱导凋亡和抑制细胞增殖有关，如生物信息学发现所揭示。此外，还公开了Oxyres治疗CRC的所有核心生物靶标和分子机制。有趣的是，可识别的MAPK1，IGF1生物靶标可能是治疗和筛选CRC的潜在分子。