Fig. 1

P-gp, BCRP and MRP1 were overexpressed in gemcitabine-resistant pancreatic cancer tissues and cells. Docking simulation revealed gemcitabine binds to the substrate binding site of P-gp, BCRP and MRP1 proteins. A IHC staining of P-gp, BCRP, MRP1 in pancreatic cancer gemcitabine-resistant and gemcitabine-sensitive tissues, 200x. Scale bar, 50 μm. B Western blotting on the expression of P-gp, BCRP, MRP1 in the indicated cells. β-actin was used as a loading control. C-H Interaction between gemcitabine and human P-gp, BCRP and MRP1 protein models. Details of the best-scoring pose of gemcitabine in the drug binding pocket of P-gp (C), BCRP (E) and MRP1 (G) binding pocket. 2D diagram of the interaction between gemcitabine and P-gp (D), BCRP (F) and MRP1 (H) binding pocket. The cavity of 20 Å was selected as the docking active region, and the docking calculation was carried out with standard parameters. Purple arrows represent hydrogen bonding, and green dash lines represent pi-pi interactions. I-N IHC staining demonstrated the P-gp (I, L), BCRP (J, M) and MRP1 (K, N) overexpression in PC tissues compared to the pancreatic non-tumor tissues. O-Q The mRNAs expression profile showed P-gp (O), BCRP (P) and MRP1 (Q) overexpression in pancreatic cancer tissue as compared to non-tumor tissue obtained from the public database (TCGA and GTEx). Data are presented as mean ± SD; *P < 0.05. IHC: immunohistochemistry