Both gemcitabine (GEM)‐resistant cell lines were more resistant to GEM in vivo. A and B, Tumors were resected from nude mouse model xenografts after different treatments (n = 5). C and D, Tumor growth was significantly inhibited by GEM in parental cells (BxPC‐3 and CFPAC‐1) compared with their corresponding GEM‐resistant cells. E, Representative histological features of BxPC‐3, BxPC‐3‐GR, CFPAC‐1, and CFPAC‐1‐GR tumors following different treatments. Red arrows indicate vacuolization formation and apoptotic features. F, Immunohistochemical staining of proliferation marker proliferating cell nuclear antigen (PCNA) in BxPC‐3, BxPC‐3‐GR, CFPAC‐1, and CFPAC‐1‐GR tumors following different treatments. Black arrows indicate positive cells. ***P < .001; comparisons indicated by lines. i.p, intraperitoneal injection; NS, no significant difference. Scale bar, 50 µm