基于meta分析和网络药理学理冲汤(丸)治疗癌症的疗效评价及作用机制研究

doi:10.5246/jcps.2023.09.059

摘要/Abstract

摘要：

理冲汤(丸)是一种具有显著抗肿瘤功效的中医处方。本研究基于meta分析和网络药理学的方法, 对理冲汤治疗癌症的疗效评价和作用机制进行了研究。首先, 采用循证医学的研究方法, 收集尽可能多的理冲汤(丸)治疗肿瘤的临床研究报告, 然后进行荟萃分析, 以确认理冲汤(丸)治疗肿瘤的疗效和安全性; 接下来, 利用网络药理学的方法预测了理冲汤(丸)对肿瘤的干预机制。Meta分析显示, 理冲汤(丸)的总有效率和安全性显著高于对照组, 具有统计学意义(P < 0.01)。理冲汤(丸)共筛选出化合物111个; 与癌症的交集靶点共339个; 由PPI网络图可知, 其核心靶点是: AKT1、TP53、TNF、IL6、JUN、VEGFA、MYC、ESR1、EGFR、CASP3; 进行GO分析, 富集基因数量最多的是protein binding, cytosol, nucleus, 分别分布了291, 179, 166个基因; KEGG分析共富集通路1894条。分子对接结果显示, 槲皮素、木犀草素、山奈酚能够很好地与AKT1、TNF、VEGFA、EGFR对接, 木犀草素-AKT1和槲皮素-AKT1结合程度最佳。发现, 理冲汤(丸)在癌症治疗中保持其疗效性和安全性; 理冲汤(丸)的有效中药成分可能通过上述多个靶点和通路, 发挥出多种生物活性来抑制癌症; 目前理冲汤(丸)治疗非妇科癌症的类型主要集中在肝细胞癌上。

关键词: 理冲汤(丸), 中医, 癌症, Meta分析, 网络药理学, 数据挖掘

Abstract:

Li Chong Decoction (Bolus) is a traditional Chinese medicine (TCM) prescription with notable antitumor efficacy. This study focused on evaluating the therapeutic efficacy and mechanism of action of Li Chong Decoction (Bolus) for cancer treatment, using meta-analysis and network pharmacology. Firstly, we adopted an evidence-based medicine research method to collect as many clinical research reports as possible on the treatment of tumors with Li Chong Decoction (Bolus). We then conducted a meta-analysis to confirm the efficacy and safety of Li Chong Decoction (Bolus) in treating tumors. Lastly, we used the network pharmacology method to predict the intervention mechanism of Li Chong Decoction (Bolus) in treating tumors. The meta-analysis showed that the total effective rate and safety of Li Chong Decoction (Bolus) were significantly higher than those of the control group (P < 0.01). From network pharmacology, we identified 111 compounds in Li Chong Decoction (Bolus) and 339 targets shared between Li Chong Decoction (Bolus) and cancer. The significant protein targets of Li Chong Decoction (Bolus) for cancer intervention were AKT1, TP53, TNF, IL6, JUN, VEGFA, MYC, ESR1, EGFR, and CASP3. GO analysis was performed, in which the entries with the highest number of enriched genes were protein binding, cytosol, and nucleus, with 291, 179, and 166 genes distributed, respectively. For KEGG analysis, 1894 channels were enriched, with pathways related to cancer among the top 20, such as pathways in cancer, prostate cancer, endocrine resistance, proteoglycans in cancer, EGFR tyrosine kinase inhibitor resistance, bladder cancer, pancreatic cancer, IL-17 signaling pathway, C-type lectin receptor signaling pathway, and hepatocellular carcinoma. Molecular docking results showed that quercetin, luteolin, and kaempferol could dock well with AKT1, TNF, VEGFA, and EGFR, and luteolin-AKT1 and quercetin-AKT1 had the best binding degree. Li Chong Decoction (Bolus) maintained its efficacy and safety in cancer treatment. The effective TCM components of Li Chong Decoction (Bolus) might inhibit cancer by targeting multiple biological processes of hub genes mentioned above. Currently, research on the treatment of non-gynecological cancers with Li Chong Decoction (Bolus) mainly focuses on hepatocellular carcinoma.

Key words: Li Chong Decoction (Bolus), Traditional Chinese medicine, Cancer, Meta-analysis, Network pharmacology, Data mining

Supporting:

张格第, 刘庚鑫, 晏子友. 基于meta分析和网络药理学理冲汤(丸)治疗癌症的疗效评价及作用机制研究[J]. 中国药学(英文版), 2023, 32(9): 720-735.

Gedi Zhang, Gengxin Liu, Ziyou Yan. Therapeutic efficacy evaluation and mechanism of action based on meta-analysis and network pharmacology of Li Chong Decoction (Bolus) for cancer treatment[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(9): 720-735.

图/表 10

Figure 1. The results of the meta-analysis. (A) Comparison of total effective rate between Li Chong Decoction (Bolus) group and control group; (B) Comparison of safety between Li Chong Decoction (Bolus) group and control group; (C) Funnel chart of total effective rate in literature publication bias; (D) Funnel chart of safety in literature publication bias.

Table 1. Compounds with degree values > 20 in Li Chong Decoction (bolus) and OB%, DL values.

Figure 2. Wayne diagram of Li Chong Decoction (Bolus) in treating tumor.

Figure 3. "Drug-component-target" network of Li Chong Decoction (Bolus) for cancer treatment.

Figure 4. PPI network of intersecting therapy targets.

Figure 5. Visualization analysis of PPI network of intersection therapy targets.

Figure 6. GO analysis of therapeutic targets of Li Chong Decoction (Bolus) for tumor intersection.

Figure 7. Enrichment analysis of KEGG pathways of tumor intersection therapy targets of Li Chong Decoction (Bolus).

Figure 8. Docking diagram of core compounds and important target molecules of Li Chong Decoction (Bolus). (A–D) Docking diagram of quercetin and AKT1, TNF, VEGFA, and EGFR targets of Li Chong Decoction (Bolus); (E–H) Docking diagram of Lluteolin and AKT1, TNF, VEGFA, and EGFR targets of Li Chong Decoction (Bolus); (I–L) Docking diagram of kaempferol and AKT1, TNF, VEGFA and EGFR targets of Li Chong Decoction (Bolus).

Table 2. The binding energy of the key components of the Li Chong Decoction (Bolus) and the target gene molecules.

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