title: Overexpression and significance of prion protein in gastric cancer and multidrug-resistant gastric carcinoma cell line SGC7901/ADR.
abstract: In our previous work, cellular prion protein (PrPc) was identified as an upregulated gene in adriamycin-resistant gastric carcinoma cell line SGC7901/ADR compared to its parental cell line SGC7901. Here we investigate the expression of PrPc in gastric cancer and whether it was involved in multidrug resistance (MDR) of gastric cancer. We demonstrated that PrPc was ubiquitously expressed in gastric cancer cell lines and tissues. PrPc conferred resistance of both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs on SGC7901, which was accompanied by decreased accumulation and increased releasing amount of adriamycin in PrPc-overexpressing cell line. Inhibition of PrPc expression by antisense or RNAi technology could partially reverse multidrug-resistant phenotype of SGC7901/ADR. PrPc significantly upregulated the expression of the classical MDR-related molecule P-gp but not multidrug resistance associated protein and glutathione S-transferase pi. The PrPc-induced MDR could be partially reversed by P-gp inhibitor verapamil. PrPc could also suppress adriamycin-induced apoptosis and alter the expression of Bcl-2 and Bax, which might be another pathway contributing to PrPc-related MDR. The further study of the biological functions of PrPc may be helpful for understanding the mechanisms of occurrence and development of clinical gastric carcinoma and PrPc-related MDR and developing possible strategies to treat gastric cancer.
authors.affiliation: Institute of Digestive Disease, Xijing Hospital, the Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, People's Republic of China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Du
authors.forename: Yanglin
authors.initials: Y
authors.lastname: Pan
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.forename: Changcun
authors.initials: C
authors.lastname: Guo
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Jin
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Taidong
authors.initials: T
authors.lastname: Qiao
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D010641:Phenotype; D018621:PrPC Proteins / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014700:Verapamil / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D002121:Calcium Channel Blockers; D018621:PrPC Proteins; D004317:Doxorubicin; D014700:Verapamil