Relationship between pokemon gene expression and drug resistance of gastric carcinoma / 第二军医大学学报

ABSTRACT

Objective To explore the relationship of pokemon gene expression and drug sensitivity and drug resistance gene in gastric cancer cells.Methods We collected the paraffin specimen of gastric cancer and para-carcinoma tissues from 60 patients with gastric cancer,detected the protein expressions of pokemon,drug resistance-associated protein P-glycoprotein (P-gp),multidrug resistance-associated protein 1 (MRP1),lung resistance protein (LRP) and survivin with immunohistochemistry (IHC) and analyzed the relationship between pokemon protein and other 4 proteins.Sulphorhodamine B (SRB) protein staining assay was performed to detect the inhibition effect of 5-fluorouracil (5-FU),cisplatin (DDP) and oxaliplatin (L-OHP) on gastric cancer cell line SGC7901,multidrug-resistant gastric carcinoma cell line SGC7901/ADR and gastric epithelial cell line GES-1,and qPCR and Western blotting were used to test expression of pokemon and drug resistance genes in the cells.Pokemon-siRNA was established and transfected into SGC7901/ADR cells,and the drug sensitivity and drug resistance genes were analyzed.Results Positive rates of pokemon,P-gp,MRP1,LRP and survivin proteins were significantly higher in gastric cancer tissues than those in para-carcinoma tissues (P＜0.05).The protein expression of pokemon was positively correlated with P-gp and survivin (r=0.385 2,P=0.002;r=0.342 4,P=0.007).Protein expressions of pokemon,P-gp,MRP1,and survivin were higher in SGC27901/ ADR cells than those in SGC7901 and GES-1 cells.The drug resistance of SGC7901/ADR cells was the strongest,followed by SGC7901,and that of GES-1 was the weakest (P＜0.01).After SGC7901/ADR cells was transfected with pokemonsiRNA,pokemon mRNA expression was significantly inhibited,mRNA and protein expressions of P-gp and survivin were decreased and the inhibitory effect of chemotherapy agents on SGC7901/ADR cells was increased (P＜0.05).Conclusion The pokemon is involved in drug resistance of gastric cancer by mutual regulation with P-gp and survivin,and pokemon may be a candidate gene for gastric cancer targeted treatment.