Clinicopathological Significance and Molecular Mechanism of AKT/GSK3β Pathway-based Fibrillin-1 Expression in Gastric Cancer Progression.

Abstract

This research was developed to explore the significance of fibrillin-1 (FBN1) in the progression of gastric cancer and its relationship with the activation of the AKT/glycogen synthase kinase-3beta (GSK3β) pathway. For this aim, immunohistochemical assays were adopted to detect FBN1 expression in chronic superficial gastritis, chronic atrophic gastritis, gastric cancer, and normal mucosa. The expression of FBN1 in gastric cancer and adjacent tissue samples was detected by reverse transcription-quantitative (RT-q) PCR and Western blot, and the relationship between FBN1 and the clinicopathological features of gastric cancer patients was analyzed. Lentivirus was utilized to construct SGC-7901 gastric cancer cell lines stably overexpressing and silencing FBN1, and the effects on cell proliferation, colony formation, and apoptosis were analyzed. AKT, GSK3β, and their phosphorylated proteins were detected by Western blot. Results showed that the positive expression rate of FBN1 increased successively in chronic superficial gastritis, chronic atrophic gastritis, and gastric cancer. FBN1 was up-regulated in gastric cancer tissues and correlated with the depth of tumor invasion. Overexpression of FBN1 promoted the proliferation and colony formation of gastric cancer cells, inhibited apoptosis, and promoted the phosphorylation of AKT and GSK3β. Silencing FBN1 expression inhibited the proliferation and clonal formation of gastric cancer cells, promoted apoptosis, and inhibited the phosphorylation of AKT and GSK3β. In conclusion, FBN1 was up-regulated in gastric cancer tissues and correlated with the depth of gastric tumor invasion. FBN1 silencing inhibited the progression of gastric cancer through the AKT/GSK3β pathway.