Banxia Xiexin Decoction Inhibits the Expression of PD-L1 Through Multi-Target and Multi-Pathway Regulation of Major Oncogenes in Gastric Cancer

Abstract

Purpose: Banxia xiexin decoction (BXXX) is a classical Chinese herbal compound for the treatment of gastrointestinal diseases. Its ingredients are also considered helpful for cancer rehabilitation. Here, we will explore the regulatory mechanism of BXXX acting on PD-L1 in gastric cancer (GC). Methods: GC samples and the general baseline data of the patients were collated. Immunohistochemical (IHC) detected the expression of programmed cell death-ligand 1(PD-L1), hypoxia-inducible factor-1 (HIF-1), epidermal growth factor receptor (EGFR), interferon-γ receptor (IFNGR) and Toll-like receptor 4 (TLR4). ELISA detected the expressions of EGF, IFNG and IL-6 in serum samples. Network tools were used to analyze the potential molecules of BXXX. In the cell experiment, CCK-8 detected the cell proliferation. Tunel detected the apoptosis. Western blot detected the expression of related proteins. In animal experiments, the tumor volume of GC-bearing mice was observed. Expression of EGF, IFNG and IL-6 in the serum of tumor-bearing GC mice were detected by ELISA. Western blot detected the expression of related proteins. Results: The expressions of PD-L1, HIF-1, EGFR, IFNGR and TLR4 in the tissues of GC patients were significantly increased, and the expressions of EGF, IFNG and IL-6 in serum were increased. The molecular results of the network tools showed that BXXX and its main components have a targeting effect on the key molecules of each pathway in the PD-L1 regulatory network. Cell experiments showed that BXXX can inhibit the expression of PD-L1, HIF-1, EGFR and TLR4, but has no significant effect on the expression of IFNGR, thus inhibiting the proliferation and promoting the apoptosis of GC cells. The results were consistent with the animal experiments on tumor-bearing gastric cancer mice. Conclusion: BXXX inhibited the expression of PD-L1 through multi-target and multipathway regulation of major oncogenes in GC, thus effect cell proliferation and apoptosis.

Bio-informatics and in Vitro Experiments Reveal the Mechanism of Schisandrin A Against MDA-MB-231 cells

“…The interaction enables PIK3R1 to the EGFR receptor, enhancing PI3K activity and promoting the phosphorylation of AKT and MMP9. In addition, MMP9 promotes the release of growth factors, thus activating the MAPK and PI3K/AKT pathways that activate MMP9 and MMP13 by regulating the negative feedback [ 41 ]. Activated MMP9 degrades the tumor basement membrane and ECM, thus promoting the formation of blood vessels and migration of tumor cells.…”

Application of traditional Chinese medicine in inhibiting the PD-L1 pathway for gastric cancer and colon cancer treatment

“…Through cellular and animal experiments, Xuan Feng et al demonstrated that BXXX exerted antitumor effects by decreasing IL-6/JAK/STAT3-mediated PD-L1 activity and improved drug sensitivity in gastric cancer cells by regulating the expression of 6-O-methylguanine-DNA methyltrans-ferase(MGMT) [ 52] . In another study by Xuan Feng, network tool analysis and experimental validation led to the conclusion that key molecules such as PD-L1, HIF-1, EFGR, IFNGR, and TLR4 in each pathway of the BXXX regulatory network have targeting effects, which was veri ed by cellular and animal experiments, nally con rming the mechanism of BXXX's multi-target and multi-pathway effects on gastric cancer [ 53] . As an ancient formula in Chinese medicine, BXXX is still used for digestive system diseases, but its composition is complex and pharmacological research is still inadequate.…”

Determining the Mechanism of Banxia Xiexin Decoction for Gastric Cancer Treatment through Network Analysis and Experimental Validation

“…10 BXD targets the PD-L1, HIF-1, EGFR, and TLR4 pathways, influencing GC cell apoptosis and proliferation. 11 Components, such as β-sitosterol, berberine, coptisine, and ginsenoside, classified based on medicinal flavor, directly or indirectly contribute to gastrointestinal disease management. 12 Network pharmacology, which integrates multiple theories, such as systems biology, proteomics, and genomics, is crucial to understanding TCM action mechanisms through a combination of data analysis, computer simulations, and information retrieval from comprehensive databases.…”

“…It significantly improves symptoms of chronic atrophic gastritis and reduces gland atrophy, intestinal metaplasia, and atypical hyperplasia of the gastric mucosa . BXD targets the PD-L1, HIF-1, EGFR, and TLR4 pathways, influencing GC cell apoptosis and proliferation . Components, such as β-sitosterol, berberine, coptisine, and ginsenoside, classified based on medicinal flavor, directly or indirectly contribute to gastrointestinal disease management …”