Knockdown of AGR2 induces cell apoptosis and reduces chemotherapy resistance of pancreatic cancer cells with the involvement of ERK/AKT axis

Abstract

BackgroundPancreatic cancer (PC), an aggressive human malignancy, presents with a striking resistance to chemotherapy. Interesting, AGR2 has been found to be upregulated in various cancers and has been found to promote the dissemination of PC cells. Thereby, a series of in-vitro experiments were performed to investigate the relationship between AGR2 and the ERK/AKT axis, and to explore whether it affects PC cells. MethodsPositive expression of AGR2 protein in the PC and paracancerous tissues collected from 138 patients with PC was detected using immunohistochemistry. After treatment with FGF2 (an ERK/AKT axis agonist), siRNA against AGR2 or their combination respectively, cell viability, chemotherapy resistance, radiotherapy resistance, migration, invasion and apoptosis in PC cells were detected using CCK8 assay, MTT assay, clone formation assay, wound healing assay, Transwell assay and flow cytometry, respectively. The expressions of AGR2 and ERK/AKT axis-related genes and proteins in tissues and cells were detected using reverse transcription quantitative polymerase chain reaction and Western blot assay. ResultsPC tissues exhibited highly-expressed AGR2 and abnormally activated ERK/AKT axis. FGF2 promoted the expression of AGR2, ERK/AKT axis activation, cell viability, chemotherapy resistance, migration and invasion, but decreased cell apoptosis in PC cells. However, knockdown of AGR2 resulted in inhibition of the ERK/AKT axis, reduced PC cell viability, chemotherapy resistance, migration and invasion but increased cell apoptosis in PC cells. ConclusionThe findings reveal that AGR2 silencing could promote cell apoptosis and inhibit cell migration, invasion and chemotherapy resistance of PC cell with the involvement of the ERK/AKT axis.