Abstract
Siteng Fang (STF) has been shown to inhibit migration, invasion, and adhesion as well as promote apoptosis in gastric cancer (GC) cells. However, whether it can reverse the multidrug resistance (MDR) of GC to chemotherapy drugs is unknown. Thus, we aimed to elucidate the mechanism of STF in reversing the MDR of GC. The chemical composition of STF and genes related to GC were obtained from the TCMNPAS(TCM Network Pharmacology Analysis System, TCMNPAS) Database, and the targets of the active ingredients were predicted using the Swiss Target Prediction Database. The obtained data were mapped to obtain the key active ingredients and core targets of STF in treating GC. The active component-target network and protein interaction network were constructed by Cytoscape and String database, and the key genes and core active ingredients were obtained. The biological functions and related signal pathways corresponding to the key targets were analyzed and then verified via molecular docking. A total of 14 core active ingredients of STF were screened, as well as 20 corresponding targets, which were mainly enriched in cancer pathway, proteoglycan synthesis, PI3K-AKT signaling pathway, and focal adhesion. Molecular docking showed that the core active ingredients related to MDR, namely quercetin and diosgenin, could bind well to the target. In summary, STF may reverse the MDR of GC and exert synergistic effect with chemotherapeutic drugs. It mediates MDR mainly through the action of quercetin and diosgenin on the PI3K/AKT signaling pathway. These findings are the first to demonstrate the molecular mechanism of STF in reversing MDR in GC, thus providing a direction for follow-up basic research.
Highlights
Gastric cancer (GC) is one of five cancers with the highest incidence in China [1]
The network pharmacology analysis system of Traditional Chinese medicine (TCM) was developed by Yang Ming, the director of Longhua Hospital Affiliated to Shanghai University of traditional Chinese Medicine (TCM Network Pharmacology Analysis System, TCMNPAS, National Computer Software Registration No 2019SR1127090) [10]
Quercetin is one of the active components of Radix Actinidiae Chinensis, and studies had shown that in addition to anti-inflammatory, antioxidant, apoptosis-inducing, and antiangiogenesis effects, quercetin has chemosensitizing effect to enhance the sensitivity of drug-resistant cells to drugs
Summary
Gastric cancer (GC) is one of five cancers with the highest incidence in China [1]. According to the National Cancer Center, the incidence and mortality of GC ranked second among malignant tumors in China in 2015, and showed an increasing trend each year [2]. The early diagnosis rate of GC in China is low; patients with GC are often diagnosed with advanced disease. Multidrug resistance (MDR) has become a common phenomenon, and it is a main reason for chemotherapy failure, making it difficult to improve the survival rate of patients with advanced GC [3]. Overcoming the MDR of GC to chemotherapy and improving the efficacy of anticancer drugs are key issues in the global medical community
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