Tanshinone IIA Suppresses the Proliferation of MGC803 Cells by Disrupting Glycolysis Under Anaerobic Conditions.

Abstract

This study aimed to investigate how Tanshinone IIA (Tan IIA) affects gastric cancer cell (MGC803) proliferation under anaerobic conditions, which are linked to drug resistance and tumor growth. The proliferation of MGC803 cells under both aerobic and anaerobic conditions in response to Tan IIA was assessed using the Cell Counting Kit-8 (CCK-8) assay. To elucidate the molecular mechanisms underlying these effects, proteomics analysis was performed following treatment with 50 µmol/L Tan IIA, focusing on alterations in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Additionally, in vitro evaluations such as glucose uptake, lactate production, and adenosine triphosphate (ATP) synthesis were employed to validate the alterations in glycolytic activity observed in anaerobic cells treated with Tan IIA. Under anaerobic conditions, Tan IIA enhanced the inhibitory effect on the proliferation of MGC803 cells. Proteomics data revealed that a total of 6629 proteins were identified and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with 2604 proteins exhibiting significant changes (fold change > 2 or < 0.5, P < 0.05). KEGG analysis highlighted the perturbation of glycolytic pathway by Tan IIA under anaerobic conditions, accompanied by reduced glucose uptake, lactate production, and ATP synthesis. Additionally, a downregulation of glycolytic enzyme expression was observed at both the mRNA and protein levels, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase A (LDHA), phosphofructokinase 2 (PFKP), and pyruvate dehydrogenase (PDH). Tan IIA inhibits the proliferation of MGC803 cells by disrupting the glycolysis under anaerobic conditions, offering a potential treatment for anaerobiosis-resistant solid tumors.