LZTS1 promotes proliferation and suppresses apoptosis by inhibiting the activation of AKT/GSK-38 signaling pathway in pancreatic cancer cells

Purpose: Pancreatic cancer is a kind of harmful human cancer, rated as the seventh leading cause of global death. Research has shown that in various cancers, the expression of Leucine zipper tumor suppressor 1 (LZTS1) has been found low, but its effects on pancreatic cancer is yet to be elucidated. In this research, the aim was to investigate the biological functions of LZTS1 and the underlying molecular mechanism in pancreatic cancer. Methods: GEPIA database was reported for the relative expression of LZTS1 in pancreatic cancer tissues and cell lines compared to normal ones. Kaplan-Meier analysis was done on GEPIA based on the previous data. Gene expression analysis was performed on human pancreatic cancer cell lines (BXPC3, CFPC-1, Panc-1, AsPC-1 and L3.6pl) as well as a normal cell line HEK-293T by employing RT-qPCR. Transfection procedure was done to up-or down-regulate the expressions of LZTS1 in Panc1 cell line. CCK-8 assay and flow cytometric method were adopted to determine cell viability and apoptosis, respectively. Protein expression levels were determined by Western blot. Results: Expressions of LZTS1 were high in both tumor tissues and cells. Patients with higher LZTS1 had lower 5-year overall survival rate compared to those with lower LZTS1. Overexpressed LZTS1 promoted proliferation and inhibited apoptosis in cancer cell lines. A significant promotion of phosphorylated level of AKT and GSK-38 proteins were achieved through the overexpression of LZTS1. Conclusion: The results from this study revealed that overexpression of LZTS1 increased cell viability and inhibited cell apoptosis, by activation of AKT/GSK-38 signaling pathway. Our findings indicated that LZTS1 might be a prognostic biomarker in pancreatic cancer.