title: Octarepeat peptides of prion are essential for multidrug resistance in gastric cancer cells.
abstract: OBJECTIVE
  In previous studies cellular prion protein (PrPc) is confirmed to be involved in multidrug resistance (MDR) of gastric cancer. Although octarepeat peptides are important functional domains of PrPc and are closely related to the transport of Cu2+/Zn2+ and antioxidative function, the significance in MDR remains unknown. We aimed to investigate the role of octarepeat peptides in gastric cancer MDR.
  
  
  METHODS
  Small interfering RNA (siRNA) against PrPc were transfected into adriamycin-resistant gastric cancer cell lines to inhibit the expression of wild type PrPc, and then constructs encoding PrPc without octarepeat peptides and PrPc without the fifth repeat peptide were transfected, respectively, to establish the cell models. In vitro drug sensitivity, cell apoptosis, measurement of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione (GSH), as well as changes in glutathione S-transferase (GST) were detected.
  
  
  RESULTS
  In vitro drug sensitivity test showed that octarepeat peptides could modulate the drug resistance of gastric cancer cells, but the deletion of the fifth repeat peptide had no effect. Specifically, the anti-apoptotic capacity of gastric cancer cells decreased significantly when the octarepeat peptides of PrPc was absent. Moreover, the activities of total SOD, Cu2+/Zn2+-SOD, GSH-Px, GSH, and GST detected in different stressing periods revealed that cells lacking octarepeat peptides of PrPc exhibited weakened responses to stress. However, absence of the fifth repeat peptide did not exert any effect on stress response.
  
  
  CONCLUSIONS
  The octarepeat peptides of prion is responsible for MDR in gastric cancer cells while the fifth repeat peptide is not.
authors.affiliation: Department of Gastroenterology, PLA. The Military General Hospital of Beijing, Beijing, China.
authors.forename: Ji Heng
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, PLA. The Military General Hospital of Beijing, Beijing, China.
authors.forename: Jing Ping
authors.initials: JP
authors.lastname: DU
authors.affiliation: Department of Gastroenterology, PLA. The Military General Hospital of Beijing, Beijing, China.
authors.forename: Shu Jun
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, PLA. The Military General Hospital of Beijing, Beijing, China.
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Zhai
authors.affiliation: Department of Gastroenterology, PLA. The Military General Hospital of Beijing, Beijing, China.
authors.forename: Xin Yan
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, PLA. The Military General Hospital of Beijing, Beijing, China.
authors.forename: Zhi Hong
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, PLA. The Military General Hospital of Beijing, Beijing, China.
authors.forename: Zi Tao
authors.initials: ZT
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, PLA. The Military General Hospital of Beijing, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018621:PrPC Proteins; D011328:Prions; D034741:RNA, Small Interfering; D005047:Etoposide; D004317:Doxorubicin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin; D005472:Fluorouracil