APS improves free fatty acid metabolism by activating AMPK and promoting translocation of FAT/CD36 in C2C12 myoblasts

AIM：To investigate the effect of Astragalus polysaccharides (APS) on the metabolism of free fatty acids (FFAs) in C2C12 myoblasts. METHODS：Cultured C2C12 myoblasts were used in the study. The viability of C2C12 myoblasts treated with FFAs at different concentrations for different time was observed by MTT assay. The concentrations of FFAs in the medium were detected by acetyl-CoA synthase (ACS)-acetyl-CoA oxidase (ACOD) method. The expression of fatty acid translocase (FAT/CD36), AMPK and p-AMPK protein was examined by Western blotting. RESULTS：FFAs decreased the viability of C2C12 myoblasts in a time- and concentration-dependent manner. Compared with FFAs group, the expression of cellular membrane FAT/CD36 and p-AMPK proteins increased in FFAs+APS group, but total AMPK and FAT/CD36 protein expression was not significantly changed. Meanwhile, the concentration of FFAs in the medium decreased and the cell viability increased in FFAs+APS group as compared with the group. CONCLUSION：APS improves the metabolism of FFAs by activating AMPK and promoting translocation of FAT/CD36 in C2C12 myoblasts.     

GLP-1 down-regulates mRNA expression of SOCS-3 and SREBP-1c in rats with nonalcoholic fatty liver disease

AIM: To investigate the effects of glucagon-like peptide-1(GLP-1) on mRNA expression of SOCS-3 and SREBP-1c in the rats with nonalcoholic fatty liver disease. METHODS: Male SD rats were randomly divided into normal control(NC) group, high fat(HF) group and HF+liraglutide(Lira) group. The rats in HF group and HF+Lira group were given high-fat diet for 16 weeks. After 12 weeks of high-fat diet feeding in HF+Lira group, Lira(600 μg·kg^-1·d^-1) was intraperitoneally injected for 4 weeks. At the end of the 16th week, the rats were killed. The pathological changes of the liver were observed under optical microscope. The serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglyceride(TG) and total cholesterol(TC) were detected by automatic biochemical analyzer. TG contents of liver were measured by GPO-PAP method. The fasting insulin(FINS) was determined by ELISA, and insulin resistance index was assessed by homeostasis mode assessment(HOMA-IR). The mRNA expression of SOCS-3 and SREBP-1c in the liver tissues was detected by RT-qPCR. RESULTS: Compared with NC group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF group were obviously increased(P<0.01). Compared with HF group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF+Lira group were all obviously decreased(P<0.05 or P<0.01). The mRNA expression of SOCS-3 and SREBP-1c in HF group was significantly higher than that in NC group(P<0.01). The mRNA expression of SOCSV3 and SREBP-1c in HF+Lira group was significantly decreased as compared with HF group(P<0.05). CONCLUSION: Liraglutide may improve the IR and reduce TG of liver through decreasing the mRNA expression of SOCS-3 and SREBP-1c, so as to play a therapeutic role in nonalcoholic fatty liver disease.     

Effects of liraglutide on adiponectin and insulin resistance in rats with non-alcoholic fatty liver disease

AIM：To investigate the effects of glucagon-like peptide 1 analog, liraglutide, on adiponectin and insulin resistance in the rats with diet-induced non-alcoholic fatty liver disease (NAFLD). METHODS：Male rats were randomly divided into 3 groups:normal diet (ND) group (n=10), high-fat diet (HFD) group (n=10), and HFD with intraperitoneal injection of liraglutide group (n=10, first 12 weeks with HFD, later 4 weeks with liraglutide). All treatments continued for 16 weeks, and then the rats were killed ethically and the blood samples and liver tissues were collected. The levels of alanine aminotransferase (ALT), fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) were detected by a biochemical automatic analyzer. The levels of free fatty acids (FFAs), fasting insulin (FINS) and adiponectin were measured by RIA and ELISA. RESULTS：Compared with HFD group, the body weight, liver index, homeostasis assessment-insulin resistance (HOMA-IR), the serum levels of TG, TC, ALT and FBG, and the liver levels of TG, TC and FFAs in the rats in liraglutide group were apparently lower, the degree of hepatic steatosis and inflammatory activity significantly decreased (P<0.05), and the level of adiponectin in the serum and liver homogenate increased ob-viously (P<0.05). The level of adiponectin in the liver homogenate was negatively correlated with the levels of FFAs in the liver homogenate. CONCLUSION:Liraglutide is beneficial for NAFLD rats to improve insulin resistance and reduce hepatic steatosis by increasing the level of adiponectin in the serum and liver tissues.     

Effect of GLP-1 on insulin resistance and PKCε in rats with nonalcoholic fatty liver disease induced by high fat diet

AIM: To observe the therapeutic effect of glucagon-like peptide 1 (GLP-1) analog on nonalcoholic fatty liver disease of rats and to investigate the underlying mechanism.METHODS: SD rats (n=21) were used to establish a nonalcoholic fatty liver disease model by feeding a high fat diet for 12 weeks, and other 11 rats were fed with a normal diet for 16 weeks. The model rats were randomly divided into 2 equal groups:one group was treated with glucagon-like peptide 1 analog (0.6 mg·kg^-1·d^-1) by intraperitoneal injection for 4 weeks, the other group using saline as a control. After treatment, fasting blood glucose, serum insulin, blood lipids, liver function and the pathological changes of the hepatic tissues were evaluated and the expression of PKCε at mRNA and protein levels in the liver tissues was detected by real-time PCR and Western blot, respectively.RESULTS: Compared with model group, the intervention of GLP-1 significantly reduced insulin resistance index (HOMA-IR), improved the liver function (P<0.05), decreased the liver index and blood lipids (P<0.05). HE staining showed obvious pathological changes of the hepatic tissues in model group, and the intervention of GLP-1 significantly reduced lipid droplets in the hepatocytes and improved the structural damage of the liver. The expression of hepatic protein kinase Cε (PKCε) at mRNA and protein levels significantly decreased which were reversed by treating with GLP-1.CONCLUSION: GLP-1 shows good therapeutic effect on nonalcoholic fatty liver disease of rats, possibly by controlling lipid metabolism and reducing insulin resistance, which may be related to PKCε expression.     

Advances in research on mechanism of CCN proteins in prevention and treatment of obesity and non-alcoholic fatty liver

CCN protein family plays a role in regulating the formation and remodeling of extracellular matrix, inflammation regulation, injury repair and so on, which is closely related to the occurrence and development of metabolic diseases. This review focuses on the mechanism of CCN proteins in obesity and non-alcoholic fatty liver. The roles of CCN proteins in the adipocyte activation, the fibrosis and inflammatory response in non-alcoholic fatty liver, and the injury repair against non-alcoholic fatty liver and its complications are introduced, providing new ideas for the study of CCN proteins in metabolic diseases such as obesity and non-alcoholic fatty liver.     

Effect of adipose differentiation-related protein on proliferation and apoptosis in H9c2 cells

AIM: To construct an adipose differentiation-related protein (ADRP) eukaryotic expression vector and to explore the effect of ADRP on apoptosis of H9c2 cells induced by palmitic acid (PA). METHODS: The ADRP gene obtained by the method of RT-PCR was cloned into pEGFP-C1 plasmid. The recombinant plasmid was transformed into E.coli DH5α for amplification. The recombinant plasmid was extracted from E.coli DH5α and transfected into H9c2 cells by Lipofectamine^TM2000. The stable transformants were selected by G418 screening. Expression of green fluorescent protein was observed under fluorescence microscope and the ADRP expression was identified by RT-qPCR and Western blotting analysis. The effect of PA on the proliferation of H9c2 cells was detected by MTT assay. The apoptotic percentage of H9c2 cells caused by PA was determined by flow cytometry. RESULTS: The eukaryotic expression vector pEGFP-C1-ADRP was successfully constructed. Green fluorescent was observed in the cells transfected with pEGFP-C1 or pEGFP-C1-ADRP under fluorescence microscope. RT-qPCR and Western blotting analysis showed that recombinant cells exhibited high mRNA and protein levels of ADRP. After treated with PA at different concentrations, the apoptosis rates and the proliferation inhibition of recombinant cells were both lower than those of the other two cells. CONCLUSION: The transfected H9c2 cells with stable ADRP expression were successfully established. The over-expression of ADRP prevents the cells from apoptosis and inhibition of proliferation caused by PA, indicating that ADRP plays a protective role in H9c2 cells.     

Effects of resveratrol on levels of ceramide via regulating miRNA-122 in treating non-alcoholic fatty liver disease

AIM: To observe the therapeutical effects of resveratrol on non-alcoholic fatty liver disease and its potential mechanism. METHODS: Male C57BL/6J mice were fed with high-fat and high-cholesterol diet to established non alcoholic fatty liver disease model, and were administrated with resveratrol at doses of 80 mg/kg and 160 mg/kg. After 4-week treatment, the blood sample was collected for determination of total cholesterol (TC) and triglyceride (TG). The liver tissues were harvested for measuring the liver lipid content. The histopathological examination were conducted with hematoxylin and eosin staining. The ceramide levels in the liver tissues were detected by HPLC-MS. The microRNA (mi-RNA)-122 levels in the liver tissues were detected by real-time PCR. The protein levels of serine palmitoyltransferase (SPT) were determined by Western blot. The HepG2 cells were cultured and divided into 5 groups:control group, model group (induced by 0.25 mmol/L oleic acid), model+resveratrol group (treated with 5 μmol/L resveratrol), miRNA-122 siRNA group and resveratrol+miRNA-122 siRNA group. Except control group, the cells in other groups were stimulated with oleic acid and incubated with respective drugs simultaneously for 24 h. The levels of TC, TG and ceramide in the cells of each group were measured. The protein levels of SPT in each group were determined by Western blot. RESULTS: In non-alcoholic fatty liver disease mice, resveratrol dose-dependently reduced the serum TC and TG levels, decreased the lipid deposition, the ceramide level and the SPT protein level, and increased the level of miRNA-122 in the liver tissues. In the in vitro study, compared with model group, resveratrol reduced the serum TC and TG levels, decreased the ceramide level, reduced the SPT protein level. Compared with control group, the levels of TC, TG and ceramide, and the protein expression of SPT were increased in miRNA-122 siRNA group. Compared with miRNA-122 siRNA group, no statistical difference of TC, TG, ceramide and protein expression of SPT in resveratrol combined miRNA-122 siRNA group was observed. CONCLUSION: Resveratrol significantly reduces lipid accumulation by reduction of miRNA-122 and ceramide levels, and decrease in SPT protein levels in the liver.     

Role of SIRT1/AMPK pathway in early intervention of Lira alleviating non-alcoholic fatty liver disease caused by high-fat diet in rats

AIM To investigate the effect of early intervention of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (Lira) on oxidative stress, glucose tolerance, hepatic steatosis and insulin resistance of the rats with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD), and to explore the role of silent information regulator 1 (SIRT1)/AMP-activated protein kinase (AMPK) signaling pathway in this process. METHODS Twenty-four male SD rats were randomly divided into normal diet (ND) group, HFD group and HFD+Lira group, with 8 rats in each group. After 1 week of adaptive feeding, the rats in HFD+Lira group were subcutaneously injected with Lira (200 μg/kg) per day at a fixed time point, while the rats in the remaining 2 groups were injected with normal saline at the same volume. During the intervention, the body weight, hair, appetite, defecation and activity of the rats were observed to adjust the dosage timely. The body weight, food intake and blood glucose were recorded weekly. Glucose tolerance test was performed at the end of the 16th week. At the end of the 18th week, hyperinsulinemic euglycemic clamp test was conducted after anesthesia. Blood was taken from the carotid artery. The liver and adipose tissues from different parts were taken after death. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and other indicators were detected. HE staining was used to observe the pathological changes of the liver tissue. Lipid accumulation in the liver tissues was observed by oil red O staining. Liver fibrosis was observed by Masson staining and Sirius red staining. Fluorescence staining for reactive oxygen species (ROS) was used to observe the oxidative stress in the liver. The expression of GLP-1 receptor in the liver was observed by immunofluorescence staining. The expression and localization of SIRT1 and phosphorylated AMPK at Thr172 [p-AMPK (Thr172)] were observed by immunohistochemical staining. The protein levels of AMPK, p-AMPK (Thr172), SIRT1, phosphorylated sterol regulatory element binding protein-1c at Ser372 [p-SREBP-1c (Ser372)], phosphorylated acetyl coenzyme A carboxylase at Ser79 [p-ACC (Ser79)], carnitine palmitoyltransferase 1A (CPT1A) and fatty acid synthase (FAS) in liver tissues were determined by Western blot. RESULTS The results of HE and oil red O staining of rat liver tissues in HFD group confirmed the structural disorder and serious lipid accumulation, while Masson and Sirius red staining showed severe fibrosis, suggesting the successful establishment of NAFLD rat model. Compared with ND group, the levels of total cholesterol (TC), triglyceride (TG), AST and ALT in serum, and the levels of malondialdehyde (MDA), TC, TG and ROS in liver tissues in HFD group were significantly increased (P<0.01), while the activity of superoxide dismutase (SOD) was decreased (P<0.01). The protein levels of p-AMPK (Thr172), SIRT1, p-SREBP-1c (Ser372), p-ACC (Ser79) and CPT1A in the liver tissues were significantly reduced (P<0.05 or P<0.01), while the expression of FAS was increased （P<0.01）. Compared with HFD group, lipid accumulation and fibrosis in the liver tissues of the rats in HFD+Lira group were significantly attenuated, the serum levels of TC, TG, AST and ALT, and MDA, TC, TG and ROS in liver tissues were markedly reduced (P<0.05 or P<0.01), while SOD activity was increased (P<0.05). The protein levels of p-AMPK (Thr172), SIRT1, p-SREBP-1c (Ser372), p-ACC (Ser79) and CPT1A in the liver tissues were significantly increased (P<0.05 or P<0.01), while the expression of FAS was decreased （P<0.01）. CONCLUSION Lira attenuates insulin resistance, oxidative stress and fibrosis, and improves liver lipid metabolism in the rats with NAFLD induced by HFD, which may be mediated by SIRT1/AMPK signaling pathway.     

Mechanisms of anti-apoptotic effects of IGF-1 and insulin in free fatty acid-treated RIN-m cells

AIM: To elucidate if the cytoprotective effects of IGF-1 and insulin on free fatty acid-treated pancreatic β cells involve alteration in NF-κB activity.METHODS: Apoptosis was characterized by morphological analysis with invert microscope as well as Hoechst 33342 staining under a fluorescence microscope.Influence of co-incubation with free fatty acid (FFA) and IGF-1 or regular insulin (RI) on NF-κB activity were determined by Western blotting.Impacts of Bay-117082,which is NF-κB inhibitor,on cytoprotective effects of IGF-1 and RI were measured by flow cytometry.RESULTS: Apoptosis measured by flow cytometry was inhibited by IGF-1 and RI and semi-quantitative determination by Western blotting showed co-incubation with FFA and IGF-1 or RI caused more potent activation of NF-κB compared with incubation with FFA solely.Furthermore,flow cytometry showed suppression of NF-κB activity abolished the cytoprotective effects of IGF-1 and RI.CONCLUSION: Our data suggest that anti-apoptotic effects of IGF-1 and regular insulin on FFA-treated RIN-m cells are mediated via NF-κB pathway.     

Role of TRIM8 in mouse cardiomyocyte apoptosis induced by high glucose and high free fatty acid

AIM: To investigate the effects of tripartite motif-containing protein 8 (TRIM8) on the apoptosis of mouse cardiomyocytes (MCMs) induced by high glucose and high free fatty acid (HGHF) and the underlying mechanism. METHODS: The MCMs were divided into normal glucose (NG) group (glucose at 5.5 mmol/L), high glucose (HG) group (glucose at 33 mmol/L), high free fatty acid (HF) group (sodium palmitate at 300 μmol/L) and HGHF group (glucose at 33 mmol/L and sodium palmitate at 300 μmol/L). The expression of TRIM8 in the MCMs was knocked down by siRNA, and the MCMs was further divided into control group, scrambled siRNA (Scra-siRNA)/PBS group, TRIM8-siRNA/PBS group, Scra-siRNA/HGHF group and TRIM8-siRNA/HGHF group. To further confirm the specific mechanism of TRIM8 in the MCM injury induced by HGHF, the MCMs were subgrouped into HGHF/DMSO group, HGHF+TRIM8-siRNA+DMSO (HGHF+Ts/DMSO) group, HGHF/ML385 group and HGHF+Ts/ML385 group. Accordingly, apoptosis was analyzed by flow cytometry, and the levels of reactive oxygen species (ROS) were measured by flow cytometry and DHE staining. The expression of TRIM8, nuclear factor E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit (GCLC), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1) at mRNA and protein levels was determined by qPCR and Western blot. RESULTS: HGHF increased the expression of TRIM8, and suppressed the expression of Nrf2, GCLC, HO-1 and NQO-1 in the MCMs (P < 0.05). Compared with Scra-siRNA/HGHF group, the intracellular ROS content and apoptotic rate were decreased in TRIM8-siRNA/HGHF group (P < 0.05). Correspondingly, the expression of the antioxidant molecule Nrf2 and its downstream genes GCLC, HO-1 and NQO-1 was increased (P < 0.05). In contrast, the addition of Nrf2 inhibitor ML385 partially reversed the inhibitory effect of TRIM8 expression knock-down on HGHF-induced apoptosis of MCMs. CONCLUSION: TRIM8 exacerbates the HGHF-induced cardiomyocyte apoptosis by modulating Nrf2 antioxidative pathway.     

Effect of blood glucose and insulin on serum free fatty acid level after gluconse loading in essential hypertension patients

AIM: To investigate the effects of internal change of serum insulin and plasma glucose levels on serum free fatty acid (FFA) concentrations after glucose loading. METHODS: Serum insulin, plasma glucose and FFA concentrations were measured simultaneously in 234 essential hypertension patients who were undergoing oral glucose tolerance test (OGTT)[including 20 cases with 2 type diabetes mellitus(DM),74 impaired glucose tolerance(IGT),140normal glucose tolerance(NGT);98 males,136 females]. RESULTS: Fasting serum FFA concentration (μmol/L) in DM (1 048.47±481.6) was higher than that in IGT (760.1±332.1) (P＜0.05) and in NGT (725.8±353.9) (P＜0.05). Compared with the NGT group, the glucose curve was elevated and the insulin releasing curve was characterized by a low response and a delayed peak in DM group. As for the FFA releasing curve, three groups showed a significantly decreasing trend, which was more evident in DM group. Serum FFA levels at 30 min, 60 min and 120 min after glucose ingestion were not significantly different between the three groups. CONCLUSIONS: Easting serum FFA levels were elevated in DM group. The absolute deficiency of insulin secretion decreased rather increased the difference of FFA level difference between DM group and IGT group, NGT group during OGTT. These results suggest the level of glucose utilization may have an important effect on serum FFA concentration.     

Interaction of polymorphisms in resistin gene promoter -420C/G,cytochromes P4501A1 gene MspI and cigarette smoking on nonalcoholic fatty liver disease

AIM: To investigate the interaction of polymorphisms of resistin gene promoter -420C/G, cytochromes P4501A1-MspI and cigarette smoking in nonalcoholic fatty liver disease (NAFLD). METHODS: The genetic polymorphisms in resistin gene promoter -420C/G and CYP1A1-MspI were analyzed by the technique of polymerase chain reaction (PCR) in peripheral blood leukocytes of 900 NAFLD cases and 900 healthy persons. RESULTS: The frequencies of -420C/G (GG) and CYP1A1-MspI (m2/m2) were 49.75% and 50.08% in NAFLD cases and 24.00% and 24.25% in healthy controls, respectively. Statistical tests showed a significant difference in the frequencies between the 2 groups (P<0.01). The risk of NAFLD with -420C/G (GG) was significantly higher than that of controls. Individuals who carried with CYP1A1-MspI (m2/m2) had a high risk of NAFLD. Combined analysis of the polymorphisms showed that the percentages of -420C/G (GG)/CYP1A1-MspI (m2/m2) in NAFLD and control groups were 39.83% and 12.83%, respectively (P<0.01). The people who carried with -420C/G (GG)/CYP1A1-MspI(m2/m2) had a high risk in NAFLD group. The cigarette smoking rate in NAFLD group was signi-ficantly higher than that in control group (P<0.01), and the statistic analysis suggested an interaction between cigarette smoking and -420C/G (GG) and CYP1A1-MspI (m2/m2), which increased the risk of NAFLD.CONCLUSION: -420C/G (GG), CYP1A1-MspI (m2/m2) and cigarette smoking are the risk factors in NAFLD. The interactions between genetic polymorphisms in -420C/G, CYP1A1- MspI (m2/m2) and cigarette smoking increase the risk of NAFLD.     

Effect of berberine on oxidative damage and the SIRT1/p53 pathway in liver tissues of NAFLD rats

AIM:To investigate the effect of berberine on oxidative damage and silent mating type information regulation 2 homolog 1 (SIRT1)/p53 pathway in the liver tissues of nonalcoholic fatty liver disease (NAFLD) rats and to explore the mechanism of berberine against NAFLD. METHODS:The male SD rats (n=24) were randomly divided into normal group, model group and berberine group (8 rats in each group). The rats in normal group was fed with normal diet, while the rats in model group and berberine group were fed with high-fat diet. The rats in berberine group was intragastrically administered with daily doses (100 mg/kg) of berberine for 16 weeks. The levels of liver total cholesterol (TC), triglyceride (TG), superoxide dismutase (SOD), malondialdehyde (MDA) and total anti-oxidant capatity (T-AOC) were measured. HE staining, oil red O straining and transmission electron microscopy were used to observe the histological changes of the livers. The protein levels of SIRT1, p53 and acetylated p53 (Ac-p53) were determined by Western blot. RESULTS:Compared with model group, the levels of liver TC, TG and MDA in berberine group were significantly reduced (P<0.05 or P<0.01), and the levels of SOD and T-AOC were significantly increased (P<0.01). The results of pathological observation showed that the lipid accumulation in the liver of berberine group was significantly attenuated. Compared with model group, the expression of SIRT1 was significantly increased and the expression of Ac-p53 was obviously reduced in berberine group (P<0.01). CONCLUSION:Berberine reduces hepatic steatosis and oxidative damage in NAFLD rats induce by high-fat diet, and this effect may be associated with regulation of the SIRT1/p53 signal pathway.     

Effects of uric acid on mitochondrial damage and Pgam5/Drp1 expression in rat kidney cells

AIM To investigate the effects of uric acid on mitochondrial damage and the expression of phosphoglycerate mutase family member 5 (Pgam5) and dynamin-related protein 1 (Drp1) in rat kidney cells. METHODS Normal rat kidney NRK-52E cells were treated with uric acid at 0.6 mmol/L. The cell viability was measured by MTT assay. The cell morphological change was observed by Hoechst 33258 staining. The apoptosis of the cells was analyzed by flow cytometry. The morphological structure of mitochondria was observed under transmission electron microscope. The expression of Pgam5 and Drp1 was examined by immunofluorescence staining. The mRNA expression of Pgam5 in mitochondria was detected by RT-qPCR. The protein expression of Pgam5 and Drp1 in the cytoplasmic matrix was determined by Western blot. RESULTS Uric acid significantly decreased the viability of NRK-52E cells, and significantly increased the apoptotic rate of the cells (P<0.01). Mitochondrial swelling, vacuolation and cristal rupture were observed after the NRK-52E cells were treated with uric acid, and the mRNA expression of Pgam5 in mitochondria was decreased significantly, while the protein expression of Pgam5 and Drp1 in the cytoplasmic matrix was increased significantly (P<0.01). CONCLUSION Uric acid intervention destroys the mitochondrial structure of rat renal cells, up-regulates the expression of Pgam5 and Drp1 in the cytoplasmic matrix, and induces apoptosis of the cells.     

Synergistic effect of decitabine and valproic acid on apoptosis and cell cycle arrest at G0/G1 phase in gastric cancer MGC-803 cells

AIM: To investigate the synergistic effect of decitabine (DCA) and valproic acid (VPA) on apoptosis and cell cycle arrest at G₀/G₁ phase in gastric cancer MGC-803 cells. METHODS: Gastric cancer MGC-803 cells were used in the study and divided into the following groups according to the treatment with different drugs for 72 h: DCA 1.5 μmol/L,DCA 3.0 μmol/L, VPA 1.5 mmol/L, DCA 1.5 μmol/L+VPA 1.5 mmol/L and DCA 3.0 μmol/L+VPA 1.5 mmol/L. The early and late apoptotic rates were detected by annexin V and PI staining. The cell cycle was also determined by flow cytometry. The relative nm23-H1 mRNA expression level was measured by real-time quantitative PCR. RESULTS: The apoptotic rates in VPA 1.5 mmol/L+DCA 1.5 μmol/L group (early: 33.58%±3.88%; late: 31.52%±4.20%) and VPA 1.5 mmol/L+DCA 3.0 μmol/L group (early: 42.61%±4.23%; late: 38.01%±3.86%), the percentages of the cells in G₀/G₁ phase in VPA 1.5 mmol/L+DCA 1.5 μmol/L group (61.55%±2.38%) and VPA 1.5 mmol/L+DCA 3.0 μmol/L group (66.75%±2.48%), and the relative nm23-H1 mRNA expression levels in VPA 1.5 mmol/L +DCA 1.5 μmol/L group (1.84±0.46) and VPA 1.5 mmol/L+DCA 3.0 μmol/L group (3.02±0.36) were all significantly higher than those in the corresponding concentrations of single drug treatment groups (P<0.01). CONCLUSION: Synergistic effect of VPA and DCA on apoptosis and cell cycle arrest in gastric cancer MGC-803 cells is possibly via inactivation of nm23-H1 gene expression.