被撤回的出版物: Physcion 8-O-β-glucopyranoside induced ferroptosis via regulating miR-103a-3p/GLS2 axis in gastric cancer (Retracted article. See vol. 305, 2022)

Aim: Gastric cancer (GC) is a common human malignancy tumor of digestive tract in worldwide. Physcion 8-O-beta-glucopyranoside (PG) exhibits anti-tumor effects in various cancer cells. This study aimed to explore the biological behavior effects of PG on GC cells, and determine its underlying mechanism. Material and methods: The effect of PG treatment on the ferroptotic GC cell death was detected by ROS level, intracellular Fe2+ level and malondialdehyde (MDA) generation in vitro. The mRNA expression was detected by RT-qPCR. The interaction between miR-103a-3p and glutaminase 2 (GLS2) were verified by dual-luciferase reporter gene assay. Cell proliferation, invasion and migration were examined by CCK-8 and Transwell assay. Western blot was used to examine the expression of GLS2, SLC1A5 and epithelial-mesenchymal transition (EMT) related proteins. We also evaluated the influence of PG on the tumor growth and metastasis in vivo. Results: PG-induced ferroptosis in GC cells through upregulating ROS level, intracellular Fe2+ level and MDA generation. Besides, PG also significantly enhanced the protein level of GLS2, which was an important transporter of glutamine to glutamate. Importantly, miR-103a-3p directly interacted with GLS2 and suppressed its expression. Mechanistically, PG treatment significantly promoted ferroptosis and anti-tumorigenesis by down-regulating inhibitory effect of miR-103a-3p on GLS2 expression. Conclusion: Our studies confirmed that PG exerts pro-ferroptosis and anti-tumor effects in vitro and in vivo through regulating miR-103a-3p/GLS2 axis, thereby highlighting its therapeutic potential in GC.