ArticleImmunity, inflammation and disease2025
Jian Pi Hua Tan Fang Reverses Trastuzumab Resistance of HER2-Positive Gastric Cancer Through PI3K/AKT/mTOR Pathway: Integrating Network Pharmacology, Molecular Docking and Experimental Validation.
Article in Immunity, inflammation and disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Molecular classification and precision therapy in gastric cancer: Current advances and future perspectives (Review).Oncology reports · 2026Review
- The impact of the PI3K/AKT/mTOR signaling pathway on trastuzumab resistance in HER2-positive gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Mechanism by which SUGT1 downregulates FH to promote proliferation and migration in serous ovarian cancer.Journal of ovarian research · 2025Article
- Huashi Jiedu Decoction Enhances 5-Fluorouracil Efficacy in Gastric Cancer via miRNA-21-3p/p53 Pathway.Drug design, development and therapy · 2025Article
- Network pharmacology analysis and experimental validation elucidate the protective mechanisms of BYHWD against hypoxia/reoxygenation-induced endothelial cell injury.Frontiers in medicine · 2025Article
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9 authors.
Funding
Abstract
backgroundCurrently, trastuzumab resistance significantly impacts the treatment outcome for individuals with HER2-positive gastric cancer. In clinical practice, Jian Pi Hua Tan Fang (JPHTF) has been shown to be effective in preventing recurrences and metastases caused by gastric cancer. Yet, the treatment process remains unknown. We aim to evaluate the potential pharmacological mechanism of JPHTF in interfering with resistance to trastuzumab in HER2-positive gastric cancer (GC).
methodsIn this study, network pharmacology and molecular docking techniques were used to forecast the potential active ingredients, pathways, and targets of JPHTF in overcoming trastuzumab resistance in HER2-positive GC. Then, in vitro models of NCI-N87/TR was developed, and JPHTF-containing serum was utilized for intervention to confirm these crucial targets.
resultsNetwork pharmacology showed that 92 potential active compounds and 420 therapeutic targets of JPHTF. SRC, EGFR, TP53, and AKT1 were identified as the main targets associated with the PI3K/Akt, MAPK, and Ras pathways, playing crucial roles in angiogenesis, cell apoptosis, cell proliferation, and resistance to chemotherapy in the GC microenvironment. Molecular docking analysis showed that quercetin, formononetin, and luteolin, which are the main active ingredients, exhibit high binding affinity to the central targets PI3K, AKT, and mTOR. In vitro experiment, the JPHTF-containing serum has a significant alleviating effect on reversing trastuzumab resistance and cell apoptotic and proliferation of NCI-N87/TR. Further molecular biological experiments showed that JPHTF could regulate the expression of PI3K/AKT/mTOR pathway.
conclusionJPHTF has the ability to overcome trastuzumab resistance in NCI-N87 cells through the regulation of the PI3K/AKT/mTOR pathway.
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