Shi Hongshuo, Tian Sisheng, Tian Hu
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
School of Management, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Evid Based Complement Alternat Med. 2021 Feb 20;2021:4652492. doi: 10.1155/2021/4652492. eCollection 2021.
Traditional Chinese medicine (TCM) believes that the pathogenic factors of colorectal cancer (CRC) are "deficiency, dampness, stasis, and toxin," and Fuzheng-Jiedu Decoction (FJD) can resist these factors. In this study, we want to find out the potential targets and pathways of FJD in the treatment of CRC and also explain from a scientific point of view that FJD multidrug combination can resist "deficiency, dampness, stasis, and toxin."
We get the composition of FJD from the TCMSP database and get its potential target. We also get the potential target of colorectal cancer according to the OMIM Database, TTD Database, GeneCards Database, CTD Database, DrugBank Database, and DisGeNET Database. Subsequently, PPI analysis, KEGG pathways analysis, and GO biological processes analysis were carried out for the target of FJD in the therapy of colorectal cancer. In addition, we have also built a relevant network diagram.
In this study, we identified four core compounds of FJD in the therapy of colorectal cancer, including quercetin, kaempferol, beta-sitosterol, and stigmasterol. At the same time, we also obtained 30 core targets, including STAT3, INS, TP53, VEGFA, AKT1, TNF, IL6, JUN, EGF, CASP3, MAPK3, MAPK1, MAPK8, SRC, IGF1, CCND1, ESR1, EGFR, PTEN, MTOR, FOS, PTGS2, CXCL8, HRAS, CDH1, BCL2L1, FN1, MMP9, ERBB2, and JAK2. FJD treatment of colorectal cancer mainly involves 112 KEGG pathways, including FoxO (hsa04068) signaling pathway, PI3K-Akt (hsa04151) signaling pathway, HIF-1 (hsa04066) signaling pathway, T cell receptor (hsa04660) signaling pathway, and ErbB (hsa04012) signaling pathway. At the same time, 330 GO biological processes were summarized, including cell proliferation, cell apoptosis, angiogenesis, inflammation, and immune.
In this study, we found that FJD can regulate cell proliferation, apoptosis, inflammation and immunity, and angiogenesis through PI3K-Akt signaling pathway to play an anti-CRC effect.
中医认为，结直肠癌（CRC）的致病因素为“虚、湿、瘀、毒”，扶正解毒汤（FJD）可对抗这些因素。在本研究中，我们旨在找出FJD治疗CRC的潜在靶点和途径，并从科学角度解释FJD多药联合可对抗“虚、湿、瘀、毒”的机制。
我们从中药系统药理学数据库（TCMSP）获取FJD的成分及其潜在靶点。同时，依据在线孟德尔人类遗传数据库（OMIM）、治疗靶点数据库（TTD）、基因卡片数据库（GeneCards）、比较毒理基因组学数据库（CTD）、药物银行数据库（DrugBank）和疾病基因数据库（DisGeNET）获取结直肠癌的潜在靶点。随后，对FJD治疗结直肠癌的靶点进行蛋白质-蛋白质相互作用（PPI）分析、京都基因与基因组百科全书（KEGG）通路分析和基因本体（GO）生物学过程分析。此外，我们还构建了相关网络图。
本研究确定了FJD治疗结直肠癌的四种核心化合物，包括槲皮素、山奈酚、β-谷甾醇和豆甾醇。同时，我们还获得了30个核心靶点，包括信号转导和转录激活因子3（STAT3）、胰岛素（INS）、肿瘤蛋白p53（TP53）、血管内皮生长因子A（VEGFA）、蛋白激酶B（AKT1）、肿瘤坏死因子（TNF）、白细胞介素6（IL6）、原癌基因c-Jun（JUN）、表皮生长因子（EGF）、半胱天冬酶3（CASP3）、丝裂原活化蛋白激酶3（MAPK3）、丝裂原活化蛋白激酶1（MAPK1）、丝裂原活化蛋白激酶8（MAPK）原癌基因酪氨酸蛋白激酶（SRC）、胰岛素样生长因子1（IGF1）、细胞周期蛋白D1（CCND1）、雌激素受体1（ESR1）、表皮生长因子受体（EGFR）、第10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）、哺乳动物雷帕霉素靶蛋白（MTOR）、原癌基因Fos（FOS）、前列腺素内过氧化物合酶2（PTGS2）、趋化因子（CXCL8）、原癌基因H-Ras（HRAS）、钙黏蛋白1（CDH1）、凋亡调节蛋白Bcl-2样蛋白1（BCL2L1）、纤连蛋白1（FN1）、基质金属蛋白酶9（MMP9）、表皮生长因子受体2（ERBB2）和Janus激酶2（JAK2）。FJD治疗结直肠癌主要涉及112条KEGG通路，包括叉头框蛋白O（FoxO，hsa04068）信号通路、磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt，hsa04151）信号通路、缺氧诱导因子1（HIF-1，hsa04066）信号通路、T细胞受体（hsa04660）信号通路和表皮生长因子受体（ErbB，hsa04012）信号通路。同时，总结出330个GO生物学过程，包括细胞增殖、细胞凋亡、血管生成、炎症和免疫。
本研究发现，FJD可通过PI3K-Akt信号通路调节细胞增殖、凋亡、炎症和免疫以及血管生成，从而发挥抗结直肠癌作用。
