Abstract
BackgroundMultidrug resistance (MDR) is a major obstacle to the treatment of gastric cancer (GC). Using a phage display approach, we previously obtained the peptide GMBP1, which specifically binds to the surface of MDR gastric cancer cells and is subsequently internalized. Furthermore, GMBP1 was shown to have the potential to reverse the MDR phenotype of gastric cancer cells, and GRP78 was identified as the receptor for this peptide. The present study aimed to investigate the mechanism of peptide GMBP1 and its receptor GRP78 in modulating gastric cancer MDR.MethodsFluorescence-activated cell sorting (FACS) and immunofluorescence staining were used to investigate the subcellular location and mechanism of GMBP1 internalization. iTRAQ was used to identify the MDR-associated downstream targets of GMBP1. Differentially expressed proteins were identified in GMBP1-treated compared to untreated SGC7901/ADR and SGC7901/VCR cells. GO and KEGG pathway analyses of the differentially expressed proteins revealed the interconnection of these proteins, the majority of which are involved in MDR. Two differentially expressed proteins were selected and validated by western blotting.ResultsGMBP1 and its receptor GRP78 were found to be localized in the cytoplasm of GC cells, and GRP78 can mediate the internalization of GMBP1 into MDR cells through the transferrin-related pathway. In total, 3,752 and 3,749 proteins were affected in GMBP1-treated SGC7901/ADR and SGC7901/VCR cells, respectively, involving 38 and 79 KEGG pathways. Two differentially expressed proteins, CTBP2 and EIF4E, were selected and validated by western blotting.ConclusionThis study explored the role and downstream mechanism of GMBP1 in GC MDR, providing insight into the role of endoplasmic reticulum stress protein GRP78 in the MDR of cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1361-3) contains supplementary material, which is available to authorized users.
Highlights
Multidrug resistance (MDR) is a major obstacle to the treatment of gastric cancer (GC)
These results demonstrate that GMBP1 and its receptor GRP78 were located in the cytoplasm of gastric cancer cells but not in the control group
Western blot and RT-PCR analyses showed that the transfection of SGC7901/ADR and SGC7901/VCR cells with the specific GRP78 small interfering RNA (siRNA) resulted in a marked inhibition of GRP78 protein expression and decreased mRNA levels compared to cells transfected with the control siRNA (p < 0.01) (Figure 2(A,B))
Summary
Multidrug resistance (MDR) is a major obstacle to the treatment of gastric cancer (GC). Using a phage display approach, we previously obtained the peptide GMBP1, which binds to the surface of MDR gastric cancer cells and is subsequently internalized. GMBP1 was shown to have the potential to reverse the MDR phenotype of gastric cancer cells, and GRP78 was identified as the receptor for this peptide. Surgery is effective for most patients, chemotherapy remains the primary treatment for advanced gastric cancer [2]; therapies often fail due to the multidrug resistance (MDR) exhibited by some cancer cells. Wang et al BMC Cancer (2015) 15:358 display approach, we analyzed a peptide, GMBP1, that was bound to the surface of MDR gastric cancer cells and that had the potential to be internalized into these cells and reverse the gastric MDR phenotype. Exploring novel agents that can reverse MDR in GC is necessary for the improvement of chemotherapy in GC patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
