Abstract
Aims In this study, the pharmacological effects and potential molecular mechanisms of evodiamine in treating gastric cancer (GC) were investigated. Methods GC cells lines of AGS and BGC-823 were treated with evodiamine at various concentrations for different times (24, 48, and 72 h). Inhibition of the proliferation of AGS and BGC-823 cells was assessed using a CCK-8 assay. The morphology of gastric cancer cells was detected by high-content screening (HCS). The apoptosis-inducing effect of evodiamine on AGS and BGC-823 cells was detected by flow cytometric analysis. Cell migration and invasion were detected by Transwell assay. The relative mRNA and protein expression levels of PTEN-mediated EGF/PI3K signaling pathways were investigated via RT-qPCR or western blotting, respectively. Results Evodiamine substantially inhibited AGS and BGC-823 cells proliferation in a dose- and time-dependent manner. Flow cytometric analysis revealed that evodiamine could induce apoptosis of AGS and BGC-823 cells in a dose-dependent manner. In addition, evodiamine inhibited AGS and BGC-823 cell migration and invasion. Mechanistically, the results demonstrated that evodiamine promoted the relative mRNA and protein expression of PTEN and decreased expression of EGF, EGFR, PI3K, AKT, p-AKT, and mTOR. Most importantly, evodiamine could effectively increase the mRNA and protein expression of PTEN and decrease the protein expression of EGF/PI3K pathway, indicating that evodiamine downregulated EGF/PI3K through the activation of PTEN pathway. Conclusion Evodiamine inhibited the directional migration and invasion of GC cells by inhibiting PTEN-mediated EGF/PI3K signaling pathway. These findings revealed that evodiamine might serve as a potential candidate for the treatment or prevention of GC.
Highlights
Gastric cancer (GC) is a malignant tumor originating from gastric mucosal epithelium
Whether evodiamine plays an antigastric cancer effect by regulating epidermal growth factor (EGF)/PI3K signaling pathways remains to be further investigated. us, this study aimed to explore the effect of evodiamine on EGF/PI3K signaling pathways, which contributed to better understanding of the anticancer mechanisms of evodiamine
When the concentration of evodiamine is 25 μM, the cell viability of AGS and BGC-823 cells could be reduced to about 60% of that of the control group. us, AGS cells and BGC-823 cells were incubated with 25 μM evodiamine for 24 h in the subsequent experiments, unless otherwise specified
Summary
Gastric cancer (GC) is a malignant tumor originating from gastric mucosal epithelium. Studies have shown that PTEN gene inactivation is closely related to cell apoptosis, cell proliferation, cell migration, and cell metastasis, resulting in association with the progression and incidence rate of gastric cancer [19, 20]. Previous study indicated that evodiamine-induced PC cell apoptosis by inhibiting PI3K/AKT and mitogen-activated protein kinase/ ERK and inhibiting the phosphorylation of signal transducer and activator of transcription activator 3 in human pancreatic cancer cells to inhibit autophagy [29], suggesting that evodiamine may be considered as a novel pancreatic cancer treatment. Whether evodiamine plays an antigastric cancer effect by regulating EGF/PI3K signaling pathways remains to be further investigated. Us, this study aimed to explore the effect of evodiamine on EGF/PI3K signaling pathways, which contributed to better understanding of the anticancer mechanisms of evodiamine Whether evodiamine plays an antigastric cancer effect by regulating EGF/PI3K signaling pathways remains to be further investigated. us, this study aimed to explore the effect of evodiamine on EGF/PI3K signaling pathways, which contributed to better understanding of the anticancer mechanisms of evodiamine
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