Erianin Inhibits Endometrial Cancer by Regulating Glutamine Metabolic Reprogramming Through ERK Signaling Pathway

Background: Endometrial cancer (EC) is recognized as one of the leading invasive gynecological malignancies globally. Glutamine metabolism is closely correlated with cancer development through various processes. In this study, we aimed to investigate the effects of erianin, a derivate from traditional Chinese medicinal herb, on EC therapy and glutamine metabolism. Methods: Human endometrial (EC) cell lines HEC-1A and Ishikawa were treated with erianin, and cell viability and migration were measured by cell counting kit 8 (CCK-8) and Transwell assay. The glutamine metabolism was determined by analyzing the levels of intracellular glutamine, α-ketoglutaric acid (α-KG) and ATP. A xenograft tumor model was established to check the in vivo effects of erianin. The changes of PI3K/AKT signaling were analyzed by western blotting assay. Results: Treatment with erianin notably suppressed the in vitro and in vivo growth of EC cells, simultaneously reduced the levels of glutamic acid, α-KG and ATP, suggesting the repressed glutamine metabolism. Moreover, activation of ERK signaling could abolish these anti-growth and anti-metabolism effects of erianin on EC. Conclusion: Erianin suppressed the glutamine metabolism and growth of EC through the ERK signaling pathway.