Zu Guo-Xiu, Sun Ke-Yun, Liu Xi-Jian, Tang Ji-Qin, Huang Hai-Liang, Han Tao
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China.
School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China.
World J Clin Oncol. 2024 Oct 24;15(10):1293-1308. doi: 10.5306/wjco.v15.i10.1293.
In China banxia xiexin decoction (BXD) has been used in treating gastric cancer (GC) for thousands of years and BXD has a good role in reversing GC histopathology, but its chemical composition and action mechanism are still unknown.
To investigate the mechanism of action of BXD against GC based on transcriptomics, network pharmacology, and experiments.
The transplanted tumor model was prepared, and the nude mouse were pathologically examined after administration, and hematoxylin-eosin staining was performed. The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry (UPLC-Q-Orbitrap MS/MS), and traditional Chinese medicines systems pharmacology platform, drug bank and the Swiss target prediction platform to predict the relevant targets, the differentially expressed genes (DEGs) of GC were screened by RNA-seq sequencing, and the overlapping targets were analyzed to obtain the key targets and pathways. Cell Counting Kit-8, apoptosis assay, cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for experiments.
All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude, with the capecitabine group and the BXD medium-dose group being the best. A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology, RNA-seq sequencing found 4767 GC DEGs, which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKt) signaling pathway. cellular experiments confirmed that BXD-containing serum and LY294002 could inhibit the proliferation of GC cells, promote apoptosis, and inhibit the migration of GC cells by decreasing the expression of , , , and in the PI3K-Akt pathway in MGC-803 expression.
BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.
在中国，半夏泻心汤（BXD）用于治疗胃癌（GC）已有数千年历史，且BXD在逆转GC组织病理学方面具有良好作用，但其化学成分和作用机制仍不清楚。
基于转录组学、网络药理学和实验研究BXD抗GC的作用机制。
制备移植瘤模型，给药后对裸鼠进行病理检查并进行苏木精-伊红染色。采用超高效液相色谱串联四极杆静电场轨道阱质谱（UPLC-Q-Orbitrap MS/MS）对BXD的活性成分进行质量控制和鉴定，并利用中药系统药理学平台、药物银行和瑞士靶点预测平台预测相关靶点，通过RNA-seq测序筛选GC的差异表达基因（DEGs），分析重叠靶点以获得关键靶点和通路。使用细胞计数试剂盒-8、凋亡检测、细胞迁移和实时荧光定量聚合酶链反应进行实验。
所有给药组均抑制了实验用裸鼠移植瘤的生长，其中卡培他滨组和BXD中剂量组效果最佳。通过UPLC-Q-Orbitrap MS/MS和网络药理学鉴定出BXD中共有29种化合物和859个潜在靶点，RNA-seq测序发现4767个GC DEGs，将其与网络药理学相结合分析得到246个潜在治疗靶点，通路结果显示BXD可能通过磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKt）信号通路抗GC。细胞实验证实，含BXD血清和LY294002可抑制GC细胞增殖，促进凋亡，并通过降低MGC-803中PI3K-Akt通路中 、 、 、 和 的表达抑制GC细胞迁移。
BXD具有抑制肿瘤生长速度和延缓GC发展的作用。其作用机制可能与PI3K-Akt信号通路的调节有关。
