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. CONCLUSION: The octarepeat peptides of prion is responsible for MDR in gastric cancer cells while the fifth repeat peptide is not.
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. CONCLUSION: The octarepeat peptides of prion is responsible for MDR in gastric cancer cells while the fifth repeat peptide is not.
Authors: Adrian P Wiegmans; Jodi M Saunus; Sunyoung Ham; Richard Lobb; Jamie R Kutasovic; Andrew J Dalley; Mariska Miranda; Caroline Atkinson; Simote T Foliaki; Kaltin Ferguson; Colleen Niland; Cameron N Johnstone; Victoria Lewis; Steven J Collins; Sunil R Lakhani; Fares Al-Ejeh; Andreas Möller Journal: JCI Insight Date: 2019-02-26
Authors: Izabella Grimaldi; Felipe Saceanu Leser; José Marcos Janeiro; Bárbara Gomes da Rosa; Ana Clara Campanelli; Luciana Romão; Flavia Regina Souza Lima Journal: J Mol Med (Berl) Date: 2022-09-03 Impact factor: 5.606