reported that SAHA exerted significant inhibitory efficiency against cellular survival, proliferation, migration and vasculogenic mimicry of pancreatic cancer cells. bottom of the catalytic cavity, and finally acetylates the histones within 2′-Deoxyguanosine transcription factors [3, 4]. Actually, SAHA is approved by US Food and Drug Administration (FDA) and limitedly applied for solid tumors . Reportedly, SAHA acts directly on MMP19 the promoter region of the thioredoxin (TRx) binding protein-2 (TBP-2) gene and up- regulates TBP-2 expression. TBP-2 protein interacts with TRx protein, which inactivates such biological functions as scavenging reactive oxygen species (ROS) and activating ribonucleotide reductases [6, 7]. You et al.  demonstrated that SAHA inhibited the growth of HeLa 2′-Deoxyguanosine cells, and induced their apoptosis, which was accompanied by PARP cleavage, caspase-3 activation, loss of mitochondrial membrane potential, and ROS production. Ding et al.  found that SAHA triggered MET and Akt phosphorylation in an HGF- independent manner. siRNA silencing of MET enhanced SAHA to induce the apoptosis of PC3 and A549 cells. Liu et al.  reported that SAHA inhibited the growth, reduced the migration and induced cell-cycle arrest, apoptosis and autophagy of paclitaxel-resistant ovarian cancer OC3/P cells. Gastric cancer continues to be one of the deadliest cancers in the world and therefore the identification of new target drugs is thus of significant importance . Yoo et al.  demonstrated that three-weekly SAHA-cisplatin regimen was feasible and recommended for further development in advanced gastric cancer. Zhou et al.  found that SAHA and enhanced the antitumor activity of oxaliplatin by reversing the oxaliplatin-induced Src activation, increasing H2AX expression, the cleavage of Caspase-3 and PARP in gastric cancer cells. Huang et al.  reported that RUNX3 was up-regulated by SAHA and increased the SAHA chemosensitivity in gastric cancer cells. Here, we observed the effects of SAHA and/or MG132 (a proteosome inhibitor) on the phenotypes of gastric cancer cells and its synergistic effects and subsequently clarified the related molecular mechanisms. To clarify the clinicopathological significance of acetyl-histones 3 and 4, their 2′-Deoxyguanosine expressions were determined in gastric cancer and non-neoplastic mucosa (NNM) by western blot or immunohistochemisty, and compared with clinicopathological parameters of gastric cancers. Finally, their inhibitory effect on tumor growth was determined in tumor-bearing nude model. RESULTS The effects of SAHA and MG132 on the phenotypes of gastric cancer cells The exposure to SAHA and MG132 suppressed the proliferation of MGC-803 and MKN28 in both concentration- and time-dependent manners with a synergistic effect (Figure ?(Figure1A,1A, p 0.05). According to PI staining, SAHA treatment induced G1 arrest, while MG132 induced G2/M arrest in MGC-803 and MKN28 cells (Figure ?(Figure1B).1B). SAHA could reciprocally weaken the effects of MG132 on cell cycle. As shown in Figure ?Figure2A,2A, the treatment with either SAHA or MG132 induced the apoptosis of MGC-803 and MKN28 cells in either concentration- dependent or synergistic manner according to Annexin-V and PI staining. It was the same for senescence, evidenced by -galactosidase staining (Figure ?(Figure2B).2B). SAHA and MG132 synergistically suppressed glycolysis and mitochondrial respiration of MKN28 cells (Figure ?(Figure2C,2C, p 0.05). Wound healing and matrigel transwell invasion assays indicated that SAHA increased cell migration and invasion at a low concentration. MG132 suppressed the 2′-Deoxyguanosine ability of gastric cancer cells to migrate and invade. MG132 ameliorated the effects of SAHA (0.6M) on migration and invasion of gastric cancer cells (Figure 3A-3C). As shown in Figure ?Figure3D,3D, 2.0M SAHA relieved the lamellipodia formation in gastric cancer cells, while MG132 didn’t. Open in a separate window Figure 1 The effects of SAHA and MG132.