18β-Glycyrrhetinic acid inhibits the proliferation and metastasis of gastric cancer by inhibiting the TCTP/AKT/P53 signaling pathway

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Abstract
18β-Glycyrrhetinic acid (18β-GA) has a therapeutic effect on gastric cancer (GC), but its mechanism of action is still unclear. We analyzed the effects of 18β-GA on the proliferation, migration and invasion of GC cells using CCK technology, colony formation assay, wound healing assay and Transwell assay. BALB/c nude mice were used to establish subcutaneous transplantation models, orthotopic transplantation models and tail vein Liver metastasis models, and GC proliferation and metastasis models were constructed using zebrafish. After continuous treatment with 18β-GA, the inhibitory effect of drug on tumor was observed in vivo. Finally, western blot, immunohistochemistry (IHC) and immunofluorescence (IF) were used to detect the expression of key proteins in the TCTP/AKT/P53 signaling pathway and the key proteins in the cell apoptosis, cell cycle and EMT signaling pathways. Our in vitro and in vivo functional experiments showed that 18β-GA treatment could inhibit GC proliferation and metastasis, and the effect of 18β-GA alone was similar to that of TCTP knockdown, while the inhibition effect of 18β-GA combined with TCTP knockdown was the best. In GC, the expression of TCTP, p-AKT and Ki67 protein was significantly decreased after treatment with 18β-GA, while the expression of P53 protein was increased. In addition, 18β-GA treatment significantly increased the protein expression levels of Bax, P27, P21 and E-Cadherin, and decreased the protein expression levels of Bcl-2, Cyclin D1, N-Cadherin and Vimentin. Therefore, 18β-GA can promote cell apoptosis by inhibiting the TCTP/AKT/P53 signaling pathway, arrest the cell cycle and inhibit the proliferation and metastasis of GC.
Funding Information
  • National Natural Science Foundation of China (82205116, 82260879, 82374261)

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