Connexin 43 upregulation by dioscin-inhibited gastric cancer metastasis by suppressing PI3K/Akt pathway

Dioscin, a natural steroidal saponin isolated from traditional Chinese medicine, is reported to possess antitumor activity against various cancers including gastric cancer (GC). GC patients are commonly found with low expression of Connexin 43 (Cx43) and activated epithelial-mesenchymal transition (EMT). The aim of this study was to investigate the mechanism of dioscin in inhibiting the proliferation, invasion, and metastasis of GC. Cell migration was detected using wound healing analysis while the invasion was used in Transwell membrane chambers. Colony-forming assays were researched for cell potential capacity in proliferation. The data of 68 GC patients treated with radical gastrectomy were collected from 2017 to 2019. The clinicopathological data were recorded for retrospective analysis. Cx43 was measured by immunohistochemistry in GC tissues from patients. EMT-related proteins and PI3K/Akt pathway-associated proteins were observed by using Western blot analysis. Dioscin inhibited the proliferation, migration, and invasion of SGC-7901 cells. Dioscin increased the expression of E-cadherin but decreased the expression of N-cadherin, vimentin, and snail-1. Besides, lower-level Cx43 is expressed in GC tissues compared with adjacent normal tissues. Additionally, dioscin downregulated the levels of p-Akt, p-mTOR, and p-PI3K. This research indicated that dioscin may inhibit EMT via increasing the expression of Cx43 and suppress the phosphorylation of PI3K/Akt signaling pathway and then inhibit the proliferation, invasion, and metastasis of GC.