• Archives of Pharmacal Research
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• v.19 no.2
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• pp.85-90
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• 1996

It has been suggested that oxygen-derived free radicals play an important role in the pathophysiology of acute gastric ulceration induced by NSAIDs and ischemia-reperfusion. Taurine is hypothetized to exert its protective effect on NSAIDs-induced gastric injury by its antioxidant properties. Protective effect of taurine on indomethacin-induced gastric mucosal lesion and its protection mechanism were investigated. Intragastric administration of 25 mg/kg of indomethacin induced hemorrhagic lesions on the glandular stomach in rats. Pretreatment with 0.25 or 0.5 g/kg of taurine one day before or for 3 days significantly reduced the gastric lesion formation and inhibited the elevation of lipid peroxide level in gastric mucosa. The luminol-dependent chemiluminescence of rat peritoneal neutrophils increased immediately after treatment of FMLP or indomethacin. Taurine (5-20 mM) inhibited chemiluminescence of neutrophils activated by FMLP. Human neutrophils (polymorphonuclear leukocytes) significantly adhered to the confluent monolayer of human umbilical vein endothelial cells (HUVEC) after coincubation with indomethacin. This neutrophil adhesion induced by indomethacin to HUVEC was prevented by taurine in a dose-dependent manner. These results indicate that the protective effect of taurine against NSAIDs-induced gastric mucosal injury is due to its antioxidant effect, which inhibits lipid peroxidation and neutrophil activation.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.2
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• pp.65-70
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• 2007

Chinese herb medicines have traditionally been used to treat or alleviate the symptom of various diseases. The rationale for use of certain herbs to certain disorder is now getting unveiled by modern technology. In the present study, we investigated whether herb mix extract(HMX), which is alleged to be useful for gastric ulcer, protects stomach from oxidative stress. Rats were allowed to normal diet with and without HMX (1, 5, 10 mg/kg) for 30 days. To induce gastric ulcer, ethanol (75%, 1.5 ml) or acidified aspirin (100 mg/kg in 0.2 N HCl) was administered by oral route in 24 h-fasted rats and examined the gastric ulceration(bleeding) by measuring the size 1 h after the treatment. Results indicated the area of gastric bleeding was significantly less in HMX fed rats than in normal diet fed ones, and it was dependent on the duration and amount of HMX. To investigate the underlying mechanism by which HMX protects stomach from oxidative stress, expression of enzymes like heme oxygenase (HO), cyclooxygenase (COX), and inducible nitric oxide (iNOS) were investigated in MKN-74 cells, where aspirin or H. pylori was introduced. The results were compared with RAW 264.7 cells to check if there's cell specificities exist. The expression of HO-1 but not COX-2, iNOS was significantly increased by HMX. Furthermore, HO-1 inhibitor, SnPP IX reduced the HO-1 activity and reversed the survival rate in HMX-treated MKN-74 cells. There's no difference between RAW 264.7 cells and MKN-74 cells. We, thus, concluded that HMX is beneficial for protection from oxidative injury, and induction of HO-1 by HMX in gastric cells is, at least, responsible for protection from oxidative stress such as ethanol, aspirin and possibly H. pylori infection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3447-3450
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• 2015

Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients and its correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-three elderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors (control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of Chinese People's Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carried out in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and the factors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results: The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC) and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the control group, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-${\pi}$ (GST-${\pi}$) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than in control group (P<0.05), while that of DNA topoisomerase $II{\alpha}$ ($TopoII{\alpha}$) expression lower than in the control group (P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlation with GST-${\pi}$ and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with $TopoII{\alpha}$ (r=-0.328, P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively (r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in the observation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) and eADM in tumor cells (r=-0.723, P=0.000; r=-0.570, P=0.000; r=-0.919, P=0.000; r=-0.781, P=0.000), but with hydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=-0.915, P=0.000; r=-0.890, P=0.000; r=-0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may be related to high COX-2 expression.

• Applied Microscopy
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• v.35 no.3
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• pp.153-163
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• 2005

This experiment was performed to evaluate the morphological responses of the gastric chief cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG (Bacillus Calmette-Guerin). Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (experimental control group and BCG treated group). In the experimental groups, each mouse was inoculated with $1x10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8{\sim}0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the last injection, each mouse was sacrificed. Pieces of the tissue were taken from the stomach, prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. The ultrathin sections were stained with uranyl acetate and lead citrate. The size of zymogen granule and the size of the mitochondrion of the gastric chief cells were observed and calculated. In the BCG treated group, most chief cells did not show any difference in ultrastructure, except that myelin figures were more frequently observed, in comparison with that of nornmal control group. The size of zymogen granule in the gastric chief cells of normal control, experimental control and BCG-treated groups were $0.98({\pm}0.108){\mu}m,\;1.05({\pm}0.092){\mu}m\;and\;0.93({\pm}0.053){\mu}m$, respectively. And the mitochondrial size of the gastric chief cells of normal control, experimental control and BCG-treated groups were $0.80({\pm}0.130){\mu}m,\;0.83({\pm}0.143){\mu}m\;and\;0.72({\pm}0.078){\mu}m$, respectively. From the above results, it was concluded that BCG may slightly suppress function of the gastric chief cells.

• Molecules and Cells
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• v.22 no.1
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• pp.65-69
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• 2006

In murine gastrointestinal myocytes muscarinic stimulation activates nonselective cation channels via a G-protein and $Ca^{2+}$-dependent pathway. We recorded inward cationic currents following application of carbachol ($I_{CCh}$) to murine gastric myocytes held at -60 mV, using the whole-cell patch-clamp method. The properties of the inward cationic currents were similar to those of the nonselective cation channels activated by muscarinic stimulation in other gastrointestinal smooth muscle cells. CCh-induced $I_{CCh}$ and spontaneous decay of $I_{CCh}$ (desensitization of $I_{CCh}$) occurred. Unlike the situation in guinea pig gastric myocytes, desensitization was not affected by varying $[EGTA]_i$. Pretreatment with the PLC inhibitor (U73122) blocked the activation of $I_{CCh}$, and desensitization of $I_{CCh}$ was attenuated in PLC ${\beta}_1$ knock-out mice. These results suggest that the desensitization of $I_{CCh}$ in murine gastric myocytes is not due to a pathway dependent on intracellular $Ca^{2+}$ but to the PLC ${\beta}_1$ pathway.

• Journal of Microbiology and Biotechnology
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• v.11 no.5
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• pp.876-879
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• 2001

${\gamma}$ -Tubulin is an essential component involved in microtubule nucleation. The present work examined whether the fast proliferation of cancer cells can be retarded by the depletion of ${\gamma}$ -tubulin expression. Two different gastric cancer cell lines and one control cell line were treated with antisence oligonucleotides complementary to the messenger RNA of ${\gamma}$ -tubulin. The$[^3H]$ -thymidine incorporation in the two gastric cancer cell lines, SNU-1 and SNU-216, was dramatically reducd by treatment with the ${\gamma}$ -tubulin antisense oligonucleotides in a dosage-dependent manner. In contrast, the control cell line, NIH/3T3, showed no significant effect from the antisense oligonucleotides even at a high concentration. The ablation of ${\gamma}$ -tubulin expression in the tumor cells resulted in an altered DNA synthesis during mitosis and it decreased the cell progression. Accordingly, the use of antisense oligonucleotides may be an effective way of inhibiting the proliferation of human gastric cancers.

• Asian-Australasian Journal of Animal Sciences
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• v.5 no.3
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• pp.527-532
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• 1992

The present paper describes temporal changes of immunohistochemical localization and quantities of carbonic anhydrase isozyme II (CA-II) prochymosin (PC) and pepsinogen (PN) in goat's abomasal mucosae during long term milk feeding. The CA-II was not detected by day 14 after birth and then became positive on day 34 in the parietal cells, suggesting that the excretion of the hydrochloric acid (HCl) begins between days 14 and 34 under a feeding condition without solid materials. The quantity of the PC in the gastric chief cells detected by the ELISA showed rapid increase from the day of birth, making a peak on day 8 and then gradually decreased with age. The decrease in quantity of PC became started during the time period when HCl excretion had not started yet. The quantities of PN in the gastric chief cells were almost stable during the whole period examined. Expressions of these gastric enzymes did not seem to be regulated by the change of feeding condition.

• Journal of Microbiology and Biotechnology
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• v.12 no.4
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• pp.664-668
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• 2002

Antioxidants either scavenge superoxide and free radicals or stimulate the detoxification mechanisms within cells, resulting in increased detoxification of free radicals formation. Hyperin, isolated from the stem of Uncaria rhynchophylla, prevented oxygen radical formation and inhibited lipid oxidation. The effective concentrations were 31.3 $\mu$M for a radical scavenging assay and 2.2 $\mu$M for a microsome assay. cDNA microarray analysis to determine which genes were modulated by hyperin found that 50 genes were upregulated and 37 genes were downregulated in SNU-668 human gastric cancer cells. Among these genes, thirteen genes that were significantly affected by hyperin were verified by RT-PCR for their effect of genetic reprogramming.

• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.91-98
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• 2003

A new series of highly water soluble platinum(II) complexes[Pt(II)(DL-2-hydroxy-3-methylbutyrate)(trans-l-1,2-dimninocyc1ohexane)] (PC-1) and [Pt(II)DL-2-hydroxy-3-methylbutyrate](cis-1,2-diaminocyclohexane)](PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared(IR), $^{13}C$-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II)complexes was tested against MKN-45, MKN/ADM and MKN/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 and PC-2 showed active against MKN-45/P, MKN/ADM and MKN/CDDP human gastric cancer cell lines, and the antitumor activity of these compounds were comparable or superior to that of cisplatin. The nephrotoxicities of PC-1 and PC-2 were found quite less then that of cisplatin using MTT and [$^3H$] thymidine uptake tests in rabbit proximal tubule cells, human kidney cortical cells human renal cortical tissues. Based on these results, these novel platinum(II) complex compounds(PC-1 ＆ PC-2) represent a valuable lead in the development of the new anticancer chemotherapeutic agents capable of improving antitumor activity and low nephrotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1241-1245
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• 2014

Cinobufacin is used clinically to treat patients with many solid malignant tumors. However, the mechanisms underlying action remain to be detailed. Our study focused on miRNAs involved in cinobufacin inhibition of GC cell proliferation. miRNA microarray analysis and real time PCR identified miR-494 as a significant cinobufacin-associated miRNA. In vivo, ectopic expression of miR-494 inhibited the proliferation and induced apoptosis of BGC-823 cells on CCK-8 and flow cytometry analysis. Further study verified BAG-1 (anti-apoptosis gene) to bea target of miR-494 by luciferase reporter assay and Western blotting. In summary, our study demonstrated that cinobufacin may inhibit the proliferation and promote the apoptosis of BGC-823 cells. Cinobufacin-associated miR-494 may indirectly be involved in cell proliferation and apoptosis by targeting BAG-1, pointing to use as a potential molecular target of cinobufacin in gastric cancer therapy.