Saikosaponin D suppresses esophageal squamous cell carcinoma via the PI3K-AKT signaling pathway.

Abstract

Saikosaponin D is the saikosaponin with the highest biological activity in Bupleurum chinense DC, which has anti-tumor effects on a variety of human tumors. In this study, we aimed to explore the SSD-induced apoptosis mechanism in ESCC cells. We predicted the targets of SSD and ESCC through several databases and analyzed the intersecting targets to identify the connections and possible pathways between proteins. We evaluated the binding activity between proteins and SSD through molecular docking. Based on the network pharmacology results, different concentrations of SSD were used to treat Eca-109 alongside Te-10 cells. The CCK-8, colony formation, wound healing, transwell, apoptosis, and western blot assays were performed to verify the inhibitory SSD impact on Eca-109 and Te-10 cells. Network pharmacology predicted 186 potential targets of SSD, and 500 targets of ESCC, along with 31 common targets, 5 core protein targets, and 94 potential pathways. Depending on molecular docking findings, SSD was closely bound to five core targets. Cellular experiments showed that SSD suppressed the Eca-109 and Te-10 cell proliferation and metastasis and enhanced apoptosis via the PI3K-AKT signaling. This study suggests SSD inhibited Eca-109 and Te-10 cell proliferation and migration by inhibiting the PI3K-AKT pathway and promoting apoptosis.