Inhibition of β-ionone on SGC-7901 cell proliferation and upregulation of metalloproteinases-1 and -2 expression

AIM:To observe the effect of β-ionone on the proliferation of human gastric adenocarcinoma cell line SGC-7901 and the inhibition of metalloproteinase.METHODS:Using growth inhibition, Zymograms assays and reverse transcription-polymerase-chain reaction (RT-PCR),we examined cell growth rates,activities of matrix metalloproteinases-2 (MMP-2) and-9 (MMP-9),and expression of metalloproteinases-1 (TIMP-1) and-2 (TIMP-2) in SGC-7901 cells after the treatment with β-ionone for 24 h and 48h, respectively.RESULTS:β-ionone had an inhibitory effect on the growth of SGC-7901 cells.Eight days after the treatment with β-ionone at concentrations of 25, 50, 100 and 200μmol/L,the inhibition rates were 25.9%, 28.2%, 74.4% and 90.1%,respectively. The IC50 value of β-ionone for SGC-7901 cells was estimated to be 89μmol/L.The effects of β-ionone on MMP-2 and MMP-9 activities in SGC-7901 cells were not observed. However,the levels of TIMP-1 and TIMP-2 transcripts were elevated in cells treated with β-ionone in a dose-dependent manner.CONCLUSION:β-ionone can inhibit the proliferation of SGC-7901 cells,upregulate the expression of TIMP-1 and TIMP-2 expression, and may influence metastasis of cancer.

Anti-neoplastic efficacy of Haimiding on gastric carcinoma and its mechanisms

AIM:To study the anti-neoplastic effect of Haimiding and its mechanisms of action.METHODS:Experiments using MIT and colony formation were carried out to study the in vitro anti-neoplastic action of Haimiding, its in vivo anti-neoplastic action was studied by observing its effect on the weight of tumors in FC mice and S180, H22 tumor bearing mice, as well as their life spans.The effect of Haimiding on cell apoptosis and different stages of cell cycles in human gastric carcinoma cells were studied by flow cytometry. Its effect on [Ca^2+]i of human gastric carcinoma cells and the source of Ca^2+ during the change of [Ca^2+]i were observed by confocal laser scanning technique.RESULTS:Haimiding showed a definite cytotoxicity to 8 human tumor cell lines, which was most prominent against BGC-823, Eca-109 and HCT-8 tumor cells. It also exhibited an obvious inhibition on colony formation of the above tumor cell lines, which was most prominent in Eca-109 tumor cells. It showed obvious inhibition on the growth of tumor in FC mice and S180 bearing mice as well as prolonged the life span of H22 bearing mice. It was able to induce apoptosis and elevate intracellular [Ca^2+]i concentration of tumor cells.The source of Ca^2+ came from both extracellular Ca^2+ influx and intracellular Ca^2+ release.CONCLUSION:Haimiding is composed of a TCM preparation and 5-flurouracil.Its anti-neoplastic potency is highly enhanced by synergism as compared with either one of its components. Its mechanisms of anti-neoplastic action can be attributed to its action to initiate apoptosis of tumor cells by opening the membrane calcium channel and inducing intracellular Ca^2+ release to elevate [Ca^2+]i of the tumor cells.

Apoptosis of human gastric adenocarcinoma cells induced by β-ionone

AIM:To investigate the effect of β-ionone on the growth and apoptosis of gastric adenocarcinoma cell line SGC-7901.METHODS: Using M-IT, fluorescence dye (Hoechst-33258),transmission electron microscopy and the TUNEL assay,we examined growth and apoptosis of SGC-7901 cells treated with β-ionone at various concentrations (i.e. 25, 50, 100 and 200μmol/L) for 24h,48h.RESULTS:The growth of SGC-7901 cells was inhibited by β-ionone. Seven days after treatment with β-ionone at four concentrations, the inhibition rates were 12.04%, 30.59%,78.25% and 94.15%, respectively. The IC50 value of β-ionone for SGC-7901 cells was estimated to be 89μmol/L.The apoptotic morphology was demonstrated in SGC-7901 cells treated with β-ionone by Hoechst-33258 staining and electron microscopy. Apoptosis was also shown in β-iononetreated SGC-7901 cells by the TUNEL assay.CONCLUSION:β-ionone can inhibit cell proliferation and induce apoptosis of SGC-7901 cells.However, the mechanism needs to be further investigated.

Development of Wistar rat model of insulin resistance

AIM: To establish a simplified and reliable animal model of insulin resistance with low cost in Wistar rats. METHODS: Wistar rats were treated with a high fat emulsion by ig for 10 d. Changes of the diets, drinking and body weight were monitored every day and insulin resistance was evaluated by hyperinsulinemic-euglycemicclamp techniques and short insulin tolerance test using capillary blood glucose. Morphologic changes of liver, fat, skeletal muscles, and pancreatic islets were assessed under light microscope. mRNA expressions of GLUT2 and α-glucosidase in small intestine epithelium, GLUT4 in skeletal muscles and Kir6.2 in beta cell of islets were determined by in situ hybridization.RESULTS: KITT was smaller in treated animals (4.5±0.9)than in untreated control Wistar rats (6.8±1.5), and so was glucose injection rate. Both adipocyte hypertrophy and large pancreatic islets were seen in high fat fed rats,but no changes of skeletal muscles and livers wereobserved. mRNA levels of GLUT2, α-glucosidase in small intestinal epithelium and Kir6.2 mRNA in beta cells of islets increased, whereas that of GLUT4 in skeletal muscles decreased in high fat fed group compared with normal control group.CONCLUSION: An insulin resistance animal model in Wistar rats is established by ig special fat emulsion.

Inhibition of small-intestinal sugar absorption mediated by sodium orthovanadate Na_3VO_4 in rats and its mechanisms

AIM: To investigate the inhibitory effects of sodium orthovanadate on small-intestinal glucose and maltose absorption in rats and its mechanism.METHODS: Normal Wistar rats were lavaged with sodium orthovanadate (16 mg/kg, 4 mg/kg and 1 mg/kg) for 6 d.Blood glucose values were measured after fasting and 0.5, 1, 1.5 and 2 h after glucose and maltose feeding with oxidation-enzyme method, α-glucosidase was abstracted from the upper small intestine, and its activity was examined.mRNA expression of α-glucosidase and glucose-transporter 2 (GLUT2) in epithelial cells of the small intestine was observed by in situ hybridization.RESULTS: Sodium orthovanadate could delay the increase of plasma glucose concentration after glucose and maltose loading, area under curve (AUC) in these groups was lower than that in control group. Sodium orthovanadate at dosages of 10 μmol/L, 100 μmol/L and 1000 μmol/L could suppress the activity of α-glucosidase in the small intestine of normal rats, with an inhibition rate of 68.18%, 87.22% and 91.91%,respectively. Sodium orthovanadate reduced mRNA expression of α-glucosidase and GLUT2 in epithelial cells of small intestine.CONCLUSION: Sodium orthovanadate can reduce and delay the absorption of glucose and maltose. The mechanism may be that it can inhibit the activity and mRNA expression of α-glucosidase, as well as mRNA expression of GLUT2 in small intestine.