Mechanism of traditional drug treatment of cancer-related ascites: through the regulation of IL-6/JAK-STAT3 pathway.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacy and Pharmacology Pub Date : 2024-11-14 DOI:10.1093/jpp/rgae111

Yehan Sun, Pengcheng Zhang, Jia Ma, Youmou Chen, Xingxing Huo, Hang Song, Yongfu Zhu

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Abstract

Context: Our clinical observation found that JiJiaoLiHuang Pill (JJLH), a classic traditional Chinese medicine (TCM) formulation, can significantly reduce the abdominal circumference of patients with malignant ascites, increase urine output, and improve the quality of life of patients, with preliminary efficacy. But, the exact mechanism is not yet clear.

Objective: Based on the above observations, the potential mechanism of action of the treatment was preliminarily explored.

Methods: We identified active ingredients by constructing a "Chinese medicine ingredient-key target-target" network, and verified them by molecular docking using AutoDock tools and PyMOL. Finally, we conducted preliminary verification of the validated pathways and targets using a mouse model of liver cancer ascites.

Results: Network pharmacology analysis obtained the top five active ingredients were quercetin, EUPATIN, kaempferol, Obtucarbamate B, and isorhamnetin and the top five key genes were SRC, HSP90AA1, MAPK1, STAT3, and PIK3CA. Molecular docking showed that all 5 active compounds were closely bound to key target genes (binding energy <-6). The animal experiment results showed that JJLH can significantly reduce abdominal circumference, increase urine output, and exhibit dose-dependent inhibition of the AQP-3/JAK-STAT-3 signaling pathway and the expression of related inflammatory factors.

Conclusions: The JJLH potentially inhibits the recurrence of liver cancer malignant ascites through the AQP-3/JAK-STAT-3 pathway and affects the prognosis of MA patients.

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传统药物治疗癌症相关腹水的机制：通过调节 IL-6/JAK-STAT3 通路。

背景：我们在临床观察中发现，中药经典方剂 "鸡血藤黄丸 "能明显缩小恶性腹水患者的腹围，增加尿量，改善患者的生活质量，具有初步疗效。但其确切机制尚不清楚：根据上述观察结果，初步探讨该疗法的潜在作用机制：方法：通过构建 "中药成分-关键靶标-靶点 "网络，确定有效成分，并利用 AutoDock 工具和 PyMOL 进行分子对接验证。最后，我们利用肝癌腹水小鼠模型对验证的通路和靶点进行了初步验证：网络药理学分析结果表明，槲皮素、EUPATIN、山柰醇、Obtucarbamate B 和异鼠李素是前五大活性成分，SRC、HSP90AA1、MAPK1、STAT3 和 PIK3CA 是前五大关键基因。分子对接显示，所有 5 种活性化合物都与关键靶基因紧密结合（结合能结论）：JJLH可通过AQP-3/JAK-STAT-3途径抑制肝癌恶性腹水的复发，并影响MA患者的预后。

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.