Abstract
BACKGROUND: Protein disulfide isomerase A6 (PDIA6), a member of the disulfide isomerase (PDI) family, has been reported to be closely associated with progression of various cancers. However, the specific effects of PDIA6 on gastric cancer (GC) remain unclear. In this study, we investigated the expression pattern and biological functions of PDIA6 in GC. MATERIALS AND METHODS: The CCK-8 assay was carried out to examine cell proliferation and cisplatin cytotoxicity. The Western blot analysis was used to measure the protein expression of PDIA6, Wnt3a and β-catenin. The xenograft tumor assay was performed to evaluate the in vivo effect of PDIA6 on GC cell proliferation and chemoresistance. RESULTS: PDIA6 was significantly elevated in GC tissues and cell lines. Down-regulation of PDIA6 inhibited GC cell proliferation and chemoresistance to cisplatin while up-regulation of PDIA6 promoted the proliferation and chemoresistance of GC cells. Besides, PDIA6 regulated the chemosensitivity of GC cells to cisplatin in vivo. Mechanically, PDIA6 served as a regulator of the Wnt/β-catenin signaling pathway by affecting the protein expression of Wnt3a and β-catenin in GC cells. Additionally, Wnt activator reversed the inhibitory effect of PDIA6 knockdown on cisplatin resistance in GC cells. CONCLUSION: These findings provided new insight into the potential role of PDIA6 as a promising target for drug resistance in GC chemotherapy.