L-Selenomethylselenocysteine Exerts Inhibitory Effects on the Progression of Esophageal Cancer by Targeting the PI3K/AKT Signaling Pathway.

Abstract

Background: Esophageal cancer is a common malignant tumor, making the search for effective treatments a critical research focus. L-methylselenocysteine (L-SeMC) has been reported to exert anticancer effects in various cancers; however, its role and underlying mechanisms in esophageal cancer remain unclear. This study aimed to investigate the anticancer effects of L-SeMC on esophageal cancer both in vitro and in vivo, and to explore its potential mechanisms of action.

Methods: For cellular studies, flow cytometry, colony formation assay, MTT assay, wound healing assay, and ROS measurement were employed. Western blotting was used to assess the expression levels of apoptotic proteins. A subcutaneous tumor xenograft model was established. The analysis included the evaluation of proteins related to the PI3K/AKT signaling pathway, TUNEL, and Ki-67 staining, as well as HE staining.

Results: L-SeMC caused cell death and, in a concentration-dependent manner, reduced the migration, invasion, and proliferation of esophageal cancer cells. Western blot analysis showed that L-SeMC was associated with a decrease in the anti-apoptotic protein Bcl-2 and an increase in the pro-apoptotic protein Bax. It also triggered the mitochondrial apoptosis pathway, promoting the activation of caspase-3 and subsequent cancer cell death induced by L-SeMC. In a dosedependent manner, L-SeMC decreased the phosphorylation of phosphatidylinositol 3-kinase (PI3K) downstream effector molecules. This suggests that L-SeMC inhibits the PI3K/AKT signaling pathway in esophageal cancer cells, contributing to its anticancer effects.

Conclusion: L-SeMC has a strong anticancer effect on human esophageal cancer cells and promotes apoptosis by inhibiting the PI3K/AKT signaling pathway, suggesting that L-SeMC may represent a novel strategy for the treatment of esophageal cancer.