Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arsenic trioxide (As2O3), used to treat human diseases for centuries in traditional Chinese medicine, has been identified as a very effective antileukaemic agent, but its effect on solid tumours which could be more suitable for clinical treatment with arsenic compounds is still unknown. In this study, we investigated the in vitro effect of As2O3 at concentrations of 0.01-1 microM against six human malignant cell lines, MGC-803, HIC, MCF-7, HeLa, BEL-7402 and A549 cells. As2O3 inhibited growth and induced apoptosis in these malignant cells at varying degrees, in a time dose-dependent manner. The most marked effects were seen in the gastric cancer cell line, MGC-803. In contrast, minimal growth inhibition and induction of apoptosis occurred in human embryonic pulmonary cells following treatment with As2O3 found at the same concentrations. Changes in intracellular Ca2+, following As2O3 treatment were measured by Ca2+ sensitive fluorescent probe Indo-1/AM in flow cytometric assays. The increase in intracellular Ca2+ correlated with the sensitivity of these cells to As2O3, possibly indicating that a critical intracellular Ca2+ signal transduction pathway could be involved in As2O3-mediated cell-death and its selectivity. The marked sensitivity of MGC-803 cells in vitro suggests that As2O3 may be a potential antigastric cancer agent.
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PMID:Induction of apoptosis and inhibition of human gastric cancer MGC-803 cell growth by arsenic trioxide. 1061 38

Monoclonal antibody (MAb) 3H11 can bind specifically to different cancer cells from different tissues. MAb 3H11 labeled with radioactive isotopes has been used clinically to detect primary cancer and metastatic cancer. Molecular cloning of the antigen recognized by MAb 3H11 is important in studying tumor occurrence and in developing new biotherapy for cancer. Using MAb 3H11, we screened cDNA library made from the human gastric cancer cell line MGC 803, which reacts with MAb 3H11, and isolated one positive clone specifically recognized by the antibody. The insert cDNA fragment was 0.5 kb. After recombining with glutathione-S-transferase expression vector pGEX-4T, the cDNA fragment could be expressed into a fusion protein that specifically reacted with MAb 3H11. Moreover, the fusion protein could competitively inhibit MAb 3H11 binding to MGC 803 cells. Based on the nucleotide sequence of the cDNA fragment, the full length of the cDNA (2156 bp) was obtained by Rapid-Amplification-cDNA-End (RACE) and nested PCR. Its reading frame was 1767 bp encoding a protein of 589 amino acids. Sequence analysis indicated that there is no highly homologous gene in the GenBank. Northern blot and RT-PCR showed that the mRNA of MAb 3H11 antigen was extensively distributed in embryonic tissue and in different cancerous tissues, but not in corresponding normal tissues. Moreover, in producing antibodies to the antigen expressed prokaryotically, we found that the immunogenicity of the antigen was low in mammalian. Thus we believe that this novel antigen acts as an expression regulator in embryo cells and regains expression in tumor cells. In addition, this antigen is characterized by low differentiation and high proliferation. Molecular function of the antigen needs to be investigated.
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PMID:Molecular cloning of a tumor-associated antigen recognized by monoclonal antibody 3H11. 1116 84

Isoliquiritigenin, which is possibly a principal anti-tumor constituent of licorice, a traditional Chinese herb, was examined for apoptosis-inducing activity in human gastric cancer MGC-803 cells. Typical morphological and biochemical features of apoptosis including cell shrinkage, chromatin condensation, DNA ladder formation, and appearance of apoptotic peaks (subG(1)) were observed in MGC-803 cells with isoliquiritigenin treatment. Using Fluo-3 and Rh123 as fluorescent probes, respectively, it was found that the intracellular free calcium concentration increased and the mitochondrial transmembrane potential (Deltapsi(m)) decreased in a dose-dependent manner in apoptotic cells. These results suggest that isoliquiritigenin induced apoptosis of MGC-803 cells through calcium- and Deltapsi(m)-dependent pathways, indicating that it is potentially useful as a natural anti-cancer agent.
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PMID:Apoptosis induced by isoliquiritigenin in human gastric cancer MGC-803 cells. 1173 22

Opposite biological effects of arsenic trioxide (As(2)O(3)) and arsacetin on the growth of human gastric cancer MGC-803 cells have been observed. Results show that As(2)O(3) inhibited the growth of MGC-803 cells by triggering apoptosis, whereas arsacetin promoted the cell proliferation and seemed to stimulate the secretion of some growth factors at the same micromolar concentrations. Further studies showed that As(2)O(3) could regulate protein tyrosine kinase activity, protein tyrosine phosphorylation, and Bcl-2 protein and upregulate p53 protein. The ability of arsacetin to promote cell proliferation is linked with causing the opposite effects on these factors. These results indicate that the opposite biological effects of As(2)O(3) and arsacetin involve different regulations of molecular mechanisms in MGC-803 cells and that arsacetin may be a potential tumor promoter.
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PMID:Opposite biological effects of arsenic trioxide and arsacetin involve a different regulation of signaling in human gastric cancer MGC-803 cells. 1183 93

We have investigated the action of oxidative stress in arsenite-induced apoptosis of human gastric cancer MGC-803 cells. Cells exhibited obvious characteristic of apoptosis following the treatment with 1.0 microM arsenite for 24 h. During the process, low concentration of arsenite significantly increased superoxide formation and lipid peroxidation, which was dose-dependent and was related to cell apoptosis induced by arsenite. The oxidant-dependent increase in intracellular [Ca(2+)] level and p53 gene expression were also observed at the same time. A phospholipase C inhibitor, 1-[6-([(17 beta)-3-methoxyestra-1,3,5,(10)-trien-17-yl]-amino)hexyl]-2,5-dione (U73122), could block the rapid transient increase in intracellular Ca(2+) levels, as well as the subsequent fragmentation of nuclear DNA. Addition of alpha-tocopherol before arsenite treatment abolished the transient increase in superoxide formation, lipid peroxidation, intracellular [Ca(2+)] levels and p53 gene expression, and furthermore could significantly inhibited the arsenite-induced apoptosis of MGC-803 cells. These results indicate that arsenite-induced oxidative stress, which stimulate cellular signaling systems, are involved in apoptosis of MGC-803 cells.
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PMID:Arsenite-induced reactive oxygen species and the repression of alpha-tocopherol in the MGC-803 cells. 1212 65

In our previous studies, we have discovered that the extract of glycyrrhiza uralensis Fisch (EGUF) can induce obvious apoptosis in gastric cancer cell Line MGC-803. Here, further investigation was carried on about the time-lapse changes of mitochondria transmembrane potential, intracellular free calcium ions, DNA electrophoresis, plasma membrane permeability and chromatin condensation during the apoptotic process of MGC-803 induced by EGUF and the influences of MPT-specific inhibitor Cyclosporin A(CsA) on these changes. Enhancement of plasma membrane permeability with PI staining, increase of intracellular free calcium ion and decrease of mitochondria transmembrane potential are early events in apoptotic cascades, prior to the appearances of apoptotic peak, chromatin condensation and DNA ladder. CsA significantly inhibited enhancement of plasma membrane permeability, change of intracellular free calcium ions and decrease of mitochondria transmembrane potential, also greatly delayed the progress of apoptosis. Thus, our results suggest that calcium and CsA-sensitive MPT is involved in the apoptosis of MGC-803 induced by EGUF.
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PMID:[Mitochondrial permeability transition pore regulates the apoptosis in MGC-803 induced by the extract of glycyrrhiza uralensis Fisch]. 1254 1

After incubation with 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA), photodynamically induced change in the cytoplasmic free calcium concentration ([Ca(2+)](i)) and its effect on cell damage were investigated in human gastric cancer (MGC-803). Fluorescence spectrophotometry measurement indicated that the photosensitization of MGC-803 by 2-BA-2-DMHA caused an increase in intracellular calcium [Ca(2+)](i), and this increase in [Ca(2+)](i) showed a dependence on the concentration of 2-BA-2-DMHA, light dose and extracellular [Ca(2+)](e). This phenomenon of intracellular calcium accumulation was further confirmed by using laser scanning confocal microscopy (LSCM). Furthermore, the results from MTT assay and flow cytometry analysis suggested that chelation of extracellular calcium by EGTA or intracellular calcium by BAPTA could inhibit photodynamically induced cell killing, while increase of [Ca(2+)](i) by thapsigargin (TG), a highly specific inhibitor of the Ca(2+)-ATPase, or by A23187, a calcium ionophore could enhance this action. Meanwhile, the nucleus morphology was also investigated by fluorescence microscopy. The results indicated that the increase in intracellular Ca(2+) concentration was responsible for 2-BA-2-DMHA photodynamically induced damage to MGC-803.
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PMID:Role of calcium in phototoxicity of 2-butylamino-2-demethoxy-hypocrellin A to human gastric cancer MGC-803 cells. 1258 63

Although the VEGF-Flk-1-pathway has been known as the major driving force of angiogenesis, new evidence has shown that VEGFR-1/Flt-1 plays important roles during the neovascularization under pathological conditions including tumor, atherosclerosis and arthritis. In search of Flt-1 receptor antagonizing peptides, we screened a phage display 12-mer-peptide library with recombinant Flt-1 protein. Seven candidate peptides were identified that specifically bound to VEGF receptor Flt-1, of which peptide F56 (WHSDMEWWYLLG) almost abolished VEGF binding to receptor Flt-1 in vitro. In vivo, F56 fused with DHFR (DHFR-F56) inhibited angiogenesis in a CAM assay. Moreover, DHFR-F56 significantly inhibited the growth of nodules of human gastric cancer cell line MGC-803 in BALB/c nude mice. Histological analyses showed that necrosis of the implanted tumor was markedly enhanced following treatment with DHFR-F56. In the severe combined immunodeficiency disease (SCID) mouse model for studying metastasis of the human breast cancer cell line BICR-H1, synthetic peptide F56 significantly inhibited tumor growth and lung metastases. Taken together, our results have demonstrated that peptide F56, as a Flt-1 receptor antagonist, fulfilled the antiangiogenic and antimetastatic effects by specifically interfering with the interaction between VEGF and receptor Flt-1. Thus, short peptide F56 may have clinical potential in tumor therapy.
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PMID:Suppression of tumor growth and metastasis by a VEGFR-1 antagonizing peptide identified from a phage display library. 1519 67

The induction of apoptosis and antiproliferation effect of cytokine-induced killer cells (CIK cells) on MGC- 803 cells and its mechanisms were studied by using a tetrazolium dye-based (MTT) assay. Morphological changes were observed by using inverted microscope, haematoxylin/eosin (HE) staining, scanning electron microscope, and transmission electron microscope. The TdT-mediated dUTP nick and labeling (TUNEL) method was used to detect the apoptosis-induced by CIK cells. The expression rate of p53, p16, C-myc, Bcl-2, and Bax proteins were studied by using immunohistochemical staining. There were significant differences according to varied effector-target ratios at the same working time (p < 0.01) and the same effector-target ratios at different working times (p < 0.01). Inverted microscope and HE staining observation showed that CIK cells were closer to the target cells and formed a typical "rose" shape. The scanning electron microscope showed that most target cells had undergone apoptosis and many "apoptotic bodies," and that transmission electron microscopy showed condensed chromatin, disintegration of the nucleolus, vacuoles in the cytoplasm, and apoptotic bodies appearing in most target cells. TUNEL analysis showed that apoptotic cells contract and turn navy blue in nuclei or perinuclei in the experimental group. The apoptotic rate was upmodulated between 5 and 14 hours and downregulated between 14 and 24 hours in the "CIK" experimental group. The expression of p53, p16, C-myc, and Bcl-2 were significantly downregulated (p < 0.01), and the expression of Bax was upregulated over the time of coculture in the "CIK" experimental group, compared to the control group. Our studies suggested that CIK cells induce apoptosis and have an antiproliferative effect on human MGC-803 gastric cancer cells. The CIK cells kill MGC-803 gastric cancer cells by inducing apoptosis in the early stage and by inducing necrosis in the late stage through the downregulating expression of p53, C-myc, and Bcl-2 and the upregulating expression of Bax.
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PMID:Studies on inducing apoptosis effects and mechanism of CIK cells for MGC-803 gastric cancer cell lines. 1586 51

In this work, our study focused on As(2)O(3) action in view point of telomere. Results showed that treatment of human gastric cancer MGC-803 cells with arsenic trioxide could cause up-regulation of telomeric repeat binding factor TRF1 and TRF2 mRNA and protein levels, and induced G2/M phase arrest and cell apoptosis. At the same time, telomere length shortening and telomerase inhibitory were not obvious. Flow cytometry measurements indicated that the increase of TRF1 and TRF2 proteins is related to oxidative stress by arsenic trioxide. Results also indicate that after arsenic trioxide treatment, p53 protein levels increased significantly and also could bind directly at the telomere t-loop junction. These findings demonstrate arsenic trioxide-induced cell cycle arrest and apoptosis might involve a novel pathway related to TRF1, TRF2 protein.
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PMID:Up-regulation of telomere-binding TRF1, TRF2 related to reactive oxygen species induced by As(2)O(3) in MGC-803 cells. 1590 16


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