ABSTRACT: The combination of chemotherapeutic modalities may be more effective in treating gastric cancer compared with any modality alone. Previous studies have demonstrated that the combination of anticancer bioactive peptides (ACBP) and oxaliplatin (OXA) significantly inhibited the growth of the gastric cancer cell line MKN?45, promoted the apoptosis of MKN?45 cells, and caused an irreversible arrest of the MKN?45 cell cycle in the G2/M phase. In the present study, an isobaric tag for relative and absolute quantitation (iTRAQ)?based quantitative proteomics technique was used to determine the effect of ACBP?OXA treatment on the proteomics profile of MKN?45 cells. Notably, a total of 6,210 proteins were detected. Proteins with a >1.2?fold change in expression (either up? or downregulation) and P<0.05 were considered to be differentially expressed. A total of 256 differentially expressed proteins were identified through alignments with different groups. Compared with the control group, MKN?45 cells treated with ACBP, OXA and ACBP?OXA exhibited 17 (10 up? and 7 downregulated), 111 (27 up? and 84 downregulated) and 128 (53 up? and 75 downregulated) differentially expressed proteins, respectively. Of the 256 differentially expressed proteins, 6 (TPX2, NUSAP1, TOP2A, YAP, MKi?67 and GPC4) were verified by the parallel reaction monitoring method, which revealed that TPX2, NUSAP1, TOP2A, YAP, MKi?67 and GPC4 expression decreased with ACBP?OXA treatment. The cellular localization, functional annotation and biological pathways of differentially expressed proteins were examined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The results indicated that ACBP?OXA may act through the ribosome or the AMP?activated protein kinase (AMPK) signaling pathway, and the AMPK signaling pathway may be an important mediator of the inhibitory effects of ACBP?OXA on MKN?45 gastric cancer cells. In summary, iTRAQ?based proteomics analysis of the effect of ACBP?OXA on MKN?45 cells may guide future therapeutic strategies for gastric cancer. In addition, the present study may help provide new insights into the therapeutic role of combined ACBP and OXA in gastric cancer.
