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

12-Lipoxygenase (12-LOX) is over-expressed in a variety of human tumors, but its exact effect on the tumorogenesis of gastric cancer remains largely obscure. To investigate the effect of 12-LOX and its inhibitor baicalein on proliferation and apoptosis of human gastric cancer, AGS cells were separately treated with 12-hydroxyeicosatetraenoic acid (12-HETE, a metabolite of 12-LOX) and baicalein. MTT assay revealed that the absorbance of the 12-HETE-treated group was significantly (P < 0.01) higher than that of control group and that the absorbance of baicalein-treated group was significantly (P < 0.01) less than that of the control group, and that 48 h after treatment the apoptosis index of the baicalein-treated group was significantly (P < 0.01) higher than that of the untreated group and was significantly (P < 0.01) lower in the 12-HETE-treated group. Western blotting analysis was used to investigate the mechanism of these effects. The results revealed that the concentration of phosphorylated ERK in cells treated with 100 nmol L(-1) 12-HETE was significantly (P < 0.05) higher than in the untreated group and that the concentration of phosphorylated ERK1/2 in cells treated with 40 micromol L(-1) baicalein was significantly (P < 0.05) lower than in the untreated group. The expression level of bcl-2 was up-regulated and down-regulated after separate treatment with 12-HETE and baicalein, respectively, and both of these effects could be blocked by PD98059. Protein kinase C (PKC) activity was increased by treatment with 12-HETE and reduced by treatment with baicalein (P < 0.05). The PKC inhibitor BIM (bisindolymaleimide-I) blocked the phosphorylation of ERK1/2 and activation of PKC induced by 12-LOX. When pretreated with BIM, the concentration of phospho-ERK1/2 or bcl-2 in the BIM + 12-HETE-treated group was significantly (P < 0.05) lower than in that treated with 12-HETE only, and the concentration in the BIM + baicalein-treated group was significantly (P < 0.05) higher than in that treated with baicalein only. On the basis of these data we conclude that, via its metabolite 12-HETE, 12-LOX abolishes proliferation of AGS cells and protect cells from apoptosis by activating the ERK1/2 pathway and, eventually, enhances expression of bcl-2. Because PKC is also involved in the activation of ERK1/2 induced by 12-LOX, 12-LOX inhibitors would be potentially powerful anticancer agents for prevention and cure of human gastric cancer.
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PMID:12-lipoxygenase induces apoptosis of human gastric cancer AGS cells via the ERK1/2 signal pathway. 1752 76

The ets-1 transcription factor plays an important role in cell proliferation, differentiation, apoptosis and tissue remodeling. Aberrant ets-1 expression correlates with aggressive tumor behavior and poorer prognosis in patients with various malignancies. This study evaluated the efficacy of double-stranded decoy oligonucleotides targeting ets-1-binding cis elements for the suppression of ets-1 in treatment of a peritoneal dissemination model of gastric cancer. In vitro, MTT assay was performed to evaluate the effect of the ets-1 decoy on cell growth. Electrophoretic mobility shift assay (EMSA) was performed to determine ets-1 activity. In vivo, the effect of the ets-1 decoy was investigated in the peritoneal dissemination nude mice model. Disseminated nodules were analyzed immunohistochemically. Ets-1 decoy, but not scrambled decoy, significantly inhibited cell growth in 2 gastric cancer cell lines, which showed overexpression of ets-1 protein by inhibiting the binding activity of ets-1. In the peritoneal dissemination model, the ets-1 decoy significantly suppressed the disseminated nodules, and tended to prolong the survival rate. PCNA index, microvessel density and VEGF expression were also reduced in peritoneal tumors treated with ets-1 decoy. Intraperitoneal injection of ets-1 decoy inhibited peritoneal dissemination of gastric cancer in a nude mice model. The results indicate that the decoy strategy for ets-1 offers a promising therapy for patients with incurable peritoneal dissemination of gastric cancer, most of which show overexpression of ets-1 protein.
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PMID:Gene therapy using ets-1 transcription factor decoy for peritoneal dissemination of gastric cancer. 1754 98

The purpose of this study was to investigate the anticancer activity of 15 traditional Chinese medicines which are usually used for tumor patients in China. The MTT (methylthiazolyldiphenyl-tetrazolium bromide) method was applied to compare the antitumoral activity of the aqueous crude extracts and the ethanol crude extracts of these drugs on six human digestive tumor cell lines: human liver carcinoma cell lines (HepG-2 and SMMC-7721), human gastric cancer cell line (BGC-823), human colon adenocarcinoma cell lines (LoVo and SW-116) and esophagus adenocarcinoma cell line (CaEs-17). Most ethanol extracts demonstrated a more powerful inhibitory effect than aqueous extracts. Their IC50 values were between 10 microg/mL and 500 microg/mL. Among these drugs, Paris polyphylla Smith showed a predominant inhibitory effect on all the cell lines with IC50 values ranging from 10 microg/mL to 30 microg/mL. The findings in this study suggested that traditional Chinese medicines, especially Paris polyphylla Smith, might have potential anticancer activity on digestive cancer and its mechanism needs further study.
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PMID:In vitro anticancer activity of aqueous extracts and ethanol extracts of fifteen traditional Chinese medicines on human digestive tumor cell lines. 1763 50

Recently, an interesting relationship between potassium channels and cancer has evolved. The aim of this study is to investigate expression of Eag1 potassium channel in gastric cancer and its role in cancer cells growth. The expression of Eag1 for gasric cancer patients and cell lines as well as gastric adenoma was investigated by immunohistochemistry and reverse transcription polymerase chain reaction. In addition, imipramine was used to identify the involvement of Eag1 in the growth of SGC-7901 and BGC-823 cells. Frequency of positive expression of Eag1 protein was 70.5% (67/95) and Eag1 mRNA was 68.2% (15/22) in gastric cancer primary tissues. Eag1 mRNA was positively expressed in two gastric cell lines. Eag1 protein and mRNA were negatively expressed in paired non-cancerous matched tissues and 5 cases of adenoma tissues. The expression level of Eag1 protein was associated with lymph node metastasis (P = 0.049) and stage (P = 0.039), but had no correlation with sex, age, differentiation grades, and other organs metastases. Imipramine significantly inhibited the proliferation of SGC-7901 and BGC-823 cells at 12 h and 24 h detected by cells number counting and MTT assay (P < 0.01). The study indicates Eag1 is aberrantly expressed in gastric cancer tissues and cell lines and associated with cancer lymph node metastasis and stage and play an important role in the proliferation of gastric cancer cells.
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PMID:Aberrant expression of Eag1 potassium channels in gastric cancer patients and cell lines. 1787 12

Recent development and clinical application of novel anticancer agents like S-1 have been reported to show a good outcome against gastric cancer (GC) with peritoneal dissemination (P). In our study, a retrospective analysis of the treatment for GC with P was performed. Since 1989, a chemosensitivity test with MTT assay (MTTA) using surgical specimen was performed to choose chemotherapy after surgery, resulting in good prognosis in patients who received drugs which were determined effective by the MTTA. Since 1999, S-1 was introduced as adjuvant chemotherapy, and, since 2002, initial treatment with S-1/CDDP was used for GC with P, suggesting a better prognostic outcome compared with previous results with ineffective chemotherapy or surgery alone. In conclusion, prognosis of GC with P has been improving by effective regimens with novel anticancer agents like S-1. Further research and clinical trials will be necessary to achieve a more satisfactory outcome with the treatment of GC with P.
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PMID:[Retrospective analysis of treatment for advanced gastric cancer with peritoneal dissemination]. 1803 17

The proteasome plays a pivotal role in controlling cell proliferation, apoptosis, and differentiation in a variety of tumor cells. Bortezomib is a boronic acid dipeptide derivative, which is a selective and potent inhibitor of the proteasome and has prominent effects in vitro and in vivo against several solid tumors. We examined the anti-proliferative and apoptotic effects of bortezomib in three gastric cancer cell lines (SNU638, MUGC-3 and MKN-28), along with its antitumor combination effects with other chemotherapeutic agents. Tumor cell growth inhibition and apoptosis was measured by MTT assay and FACS analysis, respectively. Apoptosis- and cell cycle-associated protein expression levels were measured by Western blot assay. Bortezomib induced the suppression of tumor cell growth and apoptosis in a dose-dependent manner with an inhibitory dose (ID)50 of approximately 0.5 microg/ml in all gastric cancer cell lines tested. Further combination treatment with cisplatin and docetaxel, in particular with docetaxel displayed dramatically increased tumor cell growth suppression in all three gastric cancer cell lines, as compared to single drug treatment alone. This was concomitant with the induction patterns of apoptotic cells. Bortezomib treatment increased the Bax protein expression. Moreover, combination treatment of bortezomib plus docetaxel resulted in a dramatic increase in the Bax expression. In contrast, Bcl-2 expression was decreased by combination treatment with bortezomib plus docetaxel in SNU638 cells. Finally, bortezomib, docetaxel and to a greater degree bortezomib plus docetaxel increased the expression levels of p27 proteins even without influencing p53 expression levels. Bortezomib has profound effects on tumor cell growth inhibition and induction of apoptosis in human gastric cancer cells, suggesting that bortezomib may be an effective therapeutic drug for patients with gastric cancer. Further combination studies with other chemotherapeutic drugs, in particular docetaxel showing more tumor cell growth inhibition and apoptosis suggest that combining bortezomib with docetaxel might be more effective for displaying tumor cell growth inhibitory effects in gastric cancer cells through regulation of Bcl-2, Bax and p27 proteins in vitro.
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PMID:Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapeutic agents in gastric cancer cell lines. 1835 92

To investigate the anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer, gastric cancer AGS cells were treated with luteolin and/or other chemotherapeutic agents. Cell growth was assessed by MTT assay, cell cycle and apoptosis were assessed by flow-cytometric analysis, and the expression of major proteins regulating cell cycle and apoptosis was also detected. The results showed that luteolin inhibited the growth of gastric cancer cells in a dose- and time-dependent manner. Flow cytometry revealed that the percentage of cells at G2/M phase increased dose-dependently. The protein levels of Cdc2, Cyclin B1 and Cdc25C were reduced and p21/cip1 was up-regulated after the treatment with luteolin. Furthermore, luteolin induced apoptosis in gastric cancer AGS cells. Western blotting showed that luteolin treatment significantly increased the levels of pro-apoptotic proteins, including Caspase-3, 6, 9, Bax, and p53, and decreased the levels of anti-apoptotic protein Bcl-2, thus shifting the Bax/Bcl ratio in favor of apoptosis. It was also demonstrated that a combinational treatment of cisplatin and luteolin induced more effectively cell growth inhibition, compared to cisplatin treatment alone. These findings indicate the anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer AGS cells and luteolin may be a promising candidate agent used in the treatment of gastric cancer.
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PMID:Anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer AGS cell line. 1839 71

Photodynamic therapy (PDT) shows a limited antitumor effect in treating gastrointestinal tumors because of improper light penetration or insufficient photosensitizer uptake. The aim of this study was to evaluate the cytotoxic effect of PDT combined with paclitaxel on in vitro cancer cells. In vitro photodynamic therapy was performed in gastric cancer cells (NCI-N87) and bile duct cancer cells (YGIC-6B) using verteporfin (2 ug mL(-1)) and a PTH light source (1 000 W, Oriel Co.) with 665-675 nm narrow band pass filter. Cytotoxicity was compared using the MTT assay between cancer cells treated with PDT alone or pretreated with paclitaxel (IC(25)). Apoptotic changes were evaluated using DAPI staining, DNA fragmentation analysis, Annexin V-FITC apoptosis assay, cell cycle analysis, and western blots for cytochrome c, Bax, and Bid. The PDT-induced cytotoxicity was potentiated by pretreating with low dose paclitaxel (P < 0.001). The enhanced cytotoxicity was due to an augmented apoptotic response mediated by exaggerated cytochrome c released from mitochondria, without Bax or Bid activation. These results show that paclitaxel pretreatment enhances PDT-mediated cancer therapy.
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PMID:Paclitaxel augments cytotoxic effect of photodynamic therapy using verteporfin in gastric and bile duct cancer cells. 1859 23

The present study aimed to evaluate the relationship between mTOR signaling pathway and DNA methylation in cell survival, cell cycle, gene expression and protein level on human gastric cancer cells. Human gastric cancer cell lines, MKN45 and SGC7901 were treated with 5-aza-dC, rapamycin and/or LY294002. Cell viability was analyzed by MTT. Cell cycle distribution was evaluated by flow cytometry (FCM). The transcription level of PTEN and p27 ( Kip1 ) genes was detected by using real-time PCR. Protein expressions were detected by Western blotting. We found that cell viability was moderately reduced when treated with 5-aza-dC alone, but remarkably reduced when mTOR pathway was inhibited together (P<0.01). mTOR inhibition enhances the effects of 5-aza-dC on arresting cell cycle at G2 phase in human gastric cancer cell lines. The expression of PTEN and p27 ( Kip1 ) mRNA was remarkably increased in the gastric cancer cells treated with combind drugs (P<0.01). Phosphorylation of Akt, p70S6K and 4E-BP1 were significantly reduced in the cells treated with LY294002 or RAPA (P<0.01), but we failed to find that 5-aza-dC enhance these effects. We suggested that mTOR inhibition could enhance the effects of 5-aza-dC on suppressing cell proliferation and arresting cell cycle in human gastric cancer cell lines, which might be a potential target for tumor therapy.
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PMID:Mammalian target of rapamycin pathway inhibition enhances the effects of 5-aza-dC on suppressing cell proliferation in human gastric cancer cell lines. 1862 47

Human hematopoietic cell K(562), human melenoma cell LiBr and human stomach cancer cells were exposed to ultrasound (US, 1.75 W/cm(2), 1.4, 2.16 and 2.4 MHz)in vitro in the presence or absence of hematoporphyrin (Hp, 100 microg/mL). The cell damaging effects of treatments were determined by means of the Trypan Blue dye exclusion test, MTT test and FDA test. The experimental results showed that the same cell line had different sensibilities to the US of different frequencies, and different cell line had different damage at the same acoustical radiation. The combined treatment with US and Hp enhanced greatly the cell damage, and no sensibility of insonation cells to US with Hp was observed. The cell damage tests showed that the results of MTT test corresponded well with that of Trypan Blue dye test.
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PMID:Synergistic effects of focus ultrasound with different frequency and hematoporphyrin on human tumor cells. 1872 34


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