• Journal of Gastric Cancer
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• v.6 no.3
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• pp.132-138
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• 2006

Purpose: Dopamine is a neurotransmitter, but in the GIT, the roles of dopamine are a regulator of epithelial cell proliferation, an endogenous protective factor, and a regulator of stomach cancer cell proliferation. By using two different gastric-cancer cell lines, we assessed the effects of dopamine and dopamine receptors on the proliferation of human gastric-cancer cells. Materials and Methods: To assess the effects of dopamine and dopamine receptors on the proliferation of human gastric-cancer cells, we investigated cell proliferation and the expression of D1, D2L, and D2S receptor in two gastric-cancer cell lines, SNU 601 and KCU-C2. The effects of dopamine and dopamine receptors on the level of the cell proliferation were determined by staining with an A/H/E (acridine orange, hoechst and ethidium bromide) mixture. Results: After dopamine treatment, the cell viability was significantly decreased in SNU 601 cells (P<0.05) where the D2L receptor was absent, but not in KCU-C2 cells. After treatment with raclopride, a D2 receptor antagonist, dopamine-dose-dependent inhibition of cell proliferation was observed in SNU 601 cells (P<0.05). After treatment with SCH 23390, a D1 receptor antagonist, dopamine significantly increased ceil proliferation in KCU-C2 cells (P<0.05), but inhibited ceil proliferation in SNU 601 cells (no D2L receptor). Conclusion: The dopamine signal via the D1 or the D2S receptor inhibited proliferation of gastric-cancer cells, but that via the D2L receptor increased proliferation. These results suggest that the regulatory effects of dopamine in the gastric-cancer cell proliferation may be controlled by using dopamine receptors.

• IMMUNE NETWORK
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• v.4 no.4
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• pp.244-249
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• 2004

Background: Corticotropin-Releasing Hormone (CRH), an important regulator of stress response, has a potent immunoregulatory effect with the ability to promote the growth of various cancer through CRH receptor type 1 under stress. Although the metastasized cancers through cell migration are more aggressive than the primary cancers, little is known about the effect of CRH on cell migration. Gastric cancer is prone to metastasize to other tissues and it is reported that gastric cancer is response to various stresses such as oxidative stress. Herein, we studied the relationship between CRH and gastric cancer cell migration. Methods: We used gastric cancer cell line, MKN-28 and tested the CRH receptor type 1 expression on MKN-28 by RT-PCR. To examine the change in the ability of migration by CRH in MKN-28, cells were incubated with CRH and then migration ability was measured using a cell migration assay. Results: We confirmed that CRH receptor type 1 was expressed in MKN-28 and HaCaT cells. The migration ability of MKN-28 cells was increased by CRH in a time-, dose- dependent manner. Conclusion: These data suggest that CRH increases migration ability in gastric cancer cell line and that CRH may be a critical regulator in the metastasis of gastric cancer cell.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5583-5586
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• 2014

Helicobacter pylori (H. pylori) infection induces apoptosis in gastric epithelial cells, and this occurrence may link to gastric carcinogenesis. However, the regulatory mechanism of H. pylori-induced apoptosis is not clear. MicroRNA-146a has been implicated as a key regulator of the immune system. This report describes our discovery of molecular mechanisms of microRNA-146a regulation of apoptosis in human gastric cancer cells. We found that overexpression of microRNA-146a by transfecting microRNA-146a mimics could significantly enhance apoptosis, and this upregulation was triggered by COX-2 inhibition. Furthermore, we found that microRNA-146a density was positively correlated with apoptosis rates in H. pylori-positive gastric cancer tissues and intratumoral microRNA-146a density was negatively correlated with lymph node metastasis among H. pylori-positive gastric cancer patients. Understanding the important roles of microRNA-146a in regulating cell apoptosis in H. pylori infected human gastric cancer cells will contribute to the development of microRNA targeted therapy in the future.

• Korean Journal of Pharmacognosy
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• v.49 no.3
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• pp.225-230
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• 2018

3',4'-Disenecioylkhellactone is one of khellactone-type coumarins isolated from the roots of Peucedanum japonicum Thunb. However, its pharmacological effects are still little understood. In the present study, we investigated the inhibitory effect of 3',4'-disenecioylkhellactone on growth of gastric cancer cells. 3',4'-Disenecioylkhellactone strongly suppressed cell proliferation and induced caspase-mediated apoptosis in AGS human gastric cancer cells. Analysis of phospho-antibody arrays revealed 3',4'-disenecioylkhellactone effectively suppressed signal transducer and activator of transcription 3 (STAT3) tyrosine phosphorylation. 3',4'-Disenecioylkhellactone decreased STAT3 translocation to the nucleus and expression of STAT3 target genes. In addition, we examined the level of STAT3 activation in several gastric cancer cells and found that the inhibition of STAT3 phosphorylation by 3',4'-disenecioylkhellactone was associated with gastric cancer cell proliferation. Taken together, this study provides evidence for the first time that 3',4'-disenecioylkhellactone may be a potential therapeutic agent for the prevention or treatment of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2745-2750
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• 2016

Gastric cancer is a multifactorial and complex malignant disease seen commonly worldwide. It is one of the few malignant conditions in which the etiology involves infectious agents (Helicobacter pylori), but there are many other risk factors incuding high salt intake. Its pathogenesis generally involves interactions between environmental factors and genetic disposition. It is currently onsidered that stem cells may play a central role in gastric cancer development.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.370-379
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• 2020

Econazole, a potent broad-spectrum antifungal agent and a Ca²⁺ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

• Nutrition Research and Practice
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• v.5 no.3
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• pp.185-191
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• 2011

In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with $200{\mu}g/mL$ CPE for 24 hr. CPE at various concentrations ($0-200{\mu}g/mL$) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPR exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

• Journal of Gastric Cancer
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• v.20 no.3
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• pp.300-312
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• 2020

Purpose: Circular RNAs (circRNAs) are a new class of RNA molecules whose function is largely unknown. There is a growing evidence that circRNAs play an important regulatory role in the progression of a variety of human cancers. However, the exact roles and the mechanisms of circRNAs in gastric cancer are not clear. In this study, we aimed to elucidate the mechanism of hsa_circ_0005556. Materials and Methods: Real-time quantitative polymerase chain reaction was used to detect the expression of hsa_circ_0005556, miR-4270, and matrix metalloproteinase-19 (MMP19) in gastric cancer tissues and cell lines. The expression of hsa_circ_0005556 in gastric cancer cells was silenced by lentivirus, and cell proliferation, invasion, migration, and tumorigenesis in nude mice were assessed to evaluate the function of hsa_circ_0005556 in gastric cancer. Results: The expression of hsa_circ_0005556 in gastric cancer tissues and gastric cancer cell lines was higher compared to normal controls. In vitro, the downregulation of hsa_ circ_0005556 significantly inhibited proliferation, migration, and invasion of gastric cancer cells. In vivo, the downregulation of hsa_circ_0005556 suppressed tumor growth in nude mice. Conclusions: Our study shows that the hsa_circ_0005556/miR-4270/MMP19 axis is involved in proliferation, migration, and invasion of gastric cancer cells through the competing endogenous RNA (ceRNA) mechanism.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.3
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• pp.127-140
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• 2011

Objectives : The research was conducted to confirm the effect of Acanthopanax senticosus harms(ASH) on the anti-tumor activities in AGS human gastric cancer cells. Methods : To examine the potential anti-tumor effect of ASH, we performed many experiments. After processing AGS cancer cells with varying concentrations 80% ethanol ASH extract, analyses by MTT, flow cytometer(FACS) and western blot were used. Results : AGS cancer cells showed decreased cell proliferation and increased contents of S phase when treated with ASH. Moreover, the Western blot experiment showed that ASH affected S phase cell cycle-related molecules(Cyclin A, p21 and p16) in AGS cells. ASH also inhibited EGFR-STAT3 pathway in AGS human gastric cancer cells. Conclusion : Based on these results, we observed that ASH arrested the cell cycle at S phase and inhibited the phosphorylation of EGFR and STAT3 proteins which reduce the cell cycle and the manifestation of the genes that are related to inhibiting cell growth in AGS cells. It can be concluded that ASH can be used in developing medicine for gastric cancer.

• Journal of Gastric Cancer
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• v.19 no.3
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• pp.315-328
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• 2019

Purpose: To investigate the clinical value of serum miR-221-3p and miR-122-5p expression levels in the diagnosis and prognosis of gastric cancer. Materials and Methods: Serum samples from 141 gastric cancer cases (gastric cancer group), 110 gastric polyps (gastric polyp group), and 75 healthy people (healthy control) were used to detect miR-221-3p and miR-122-5p expression using real-time reverse transcription polymerase chain reaction. Results: Serum miR-221-3p expression was significantly higher in the gastric cancer group than in the gastric polyp group, and it was significantly lower than that before operation. The miR-221-3p expression was significantly higher in the death group than in the survival group. The proliferation and migration ability significantly increased and the apoptosis rate significantly decreased by miR-221-3p transfection in gastric cancer cells. In contrast, the function of miR-122-5p in gastric cancer cells was opposite of miR-221-3p. Serum miR-221-3p expression was negatively correlated with that of miR-122-5p in gastric cancer. Serum miR-221-3p and miR-122-5p expressions were significantly correlated with the degree of differentiation, tumor, node, metastasis stage, lymph node metastasis, and invasion depth. miR-221-3p and miR-122-5p expression levels were independent prognostic factors for postoperative gastric cancer. In the diagnosis and predicting prognosis of gastric cancer, receiver operating characteristic analysis revealed that the area under curve of combined detection of serum miR-221-3p and miR-122-5p expression had a greater diagnostic effect than either single maker. Conclusions: The miR-221-3p and miR-122-5p are involved in the development of gastric cancer, and they have important clinical values in gastric cancer diagnosis and prognosis.