Silencing GS Homeobox 2 Alleviates Gemcitabine Resistance in Pancreatic Cancer Cells by Activating SHH/GLI1 Signaling Pathway

This study evaluates the role of GSH2 in the development and drug resistance of pancreatic cancer. Both cell culture and xenograft mouse model were used. Immunohistochemistry, Western blotting and quantitative RT-PCR were used to examine the expression of GSH2 and other related molecules. CCK8 assay was used to test the cell proliferation, and flow cytometry used to examine cell apoptosis upon gemcitabine treatment. It was found that GSH2 is overexpressed in human pancreatic cancer tissues and cells. The expression of SHH and GLI1 was reversely correlated with GSH2 in pancreatic cancer cells. SHH and GLI1 have protein –protein interactions with GSH2. GSH2 silencing in pancreatic cancer cells inhibited cell proliferation, migration and invasion, increased cell apoptosis and sensitized pancreatic cancer cells to gemcitabine treatment. Furthermore, in vivo study demonstrated that silencing GSH2 increased the effic acy of gemcitabine-based treatment. Our results indicate that GSH2 is overexpressed in pancreatic cancer. GSH2 silencing in pancreatic cancer alleviates gemcitabine resistance by activating SHH/GLI1 pathway. Thus, targeting GSH2 in PDAC could be a novel cancer therapeutic strategy.
Source: Digestive Diseases and Sciences - Category: Gastroenterology Source Type: research