Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphatidylinositol 3-kinase/AKT1 pathway was an important intracellular pathway that was frequently activated in cancer cells. In the present study, we constructed the siRNA eukaryotic expression vectors of AKT1 and transfected them into AGS cells to examine whether the down-regulation of AKT1 increased cell sensitivity towards chemotherapeutic drugs. After transfection, the expression of AKT1 was dramatically decreased in AKT1 siRNA transfectants compared with that in parental cells and empty vector control cells. The down-regulation of AKT1 could significantly enhance the sensitivity of AGS cells to vincristine, adriamycin, 5-fludrouracil and cisplatin. AKT1 siRNA could significantly down-regulate the expression of Bcl-2, and up-regulate the expression of Bax, but not alter the expression of PTEN in gastric cancer cells. These observations suggested that the siRNA constructs of AKT1 we obtained could effectively down-regulate the expression of AKT1 and reverse the resistant phenotype of gastric cancer cells. The further study of the biological functions of AKT1 may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and developing possible strategies to treat gastric cancer.
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PMID:Reversal of multidrug resistance of gastric cancer cells by downregulation of Akt1 with Akt1 siRNA. 1731 Aug 52

Apoptosis and the genes regulating this process have recently become a focus of interest in the study of cancer development and progression. Both Bcl-2 and Bax are transcriptional targets for the tumor supressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. The coordinate performance of these molecules is crucial for controlling life or death of a cell. Correlations between apoptosis and protein expression of genes controlling this process including Bcl-2, Bax and p53 in gastric cancer were here investigated with gastric tumor samples of forty patients . DNA ploidy pattern was analyzed using flow cytometry and Bcl-2, Bax, and p53 were immunohistochemically localized using specific monoclonal antibodies. In addition, serum Bcl-2 protein was estimated by enzyme linked immunosorbant assay (ELISA). The obtained data showed that the mean serum Bcl-2 protein concentration demonstrated a significant increase (P<0.0001) in positive cases (61.5+/-11.0 unit/ml) compared to the negative ones (47.5+/-3.5 unit/ml). Serum Bcl-2 protein positivity was detected in 13/40 of gastric cancer patients. Immunohistochemical positivity for Bcl-2, Bax, and p53 was shown in 45%, 68%, and 63% of samples, respectively. Positive Bcl-2 and p53 immunostaining was significantly linked with the histological grade (P<0.02 and P<0.009 respectively) and lymph duct invasion (P<0.02 and P<0.001 ). On the other hand, Bax was significantly differed with lymph duct invasion and the ploidy pattern (P<0.03 and P<0.002). In conclusion, the apoptosis-related genes p53, Bcl-2, and Bax are all linked to the occurrence of gastric cancer. Therefore, analysis of their expressions may add useful information concerning tumor behavior.
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PMID:Apoptosis dysregulation in human gastric carcinomas: relationship to anti- and pro-apoptotic protein expression. 1747 70

To investigate the influence of B-RAF-specific RNA interference on the proliferation and apoptosis of gastric cancer BGC823 cell line. B-RAF-siRNA and scramble-siRNA were synthesized and transfected into BGC823 cells by TransMessenger. The expression of B-RAF gene and Bcl-2 gene in BGC823 cells was detected by RT-PCR and the level of apoptosis was evaluated in transfected cells by flow cytometry. Results showed that TransMessenger could effectively transfect B-RAF-siRNA and scramble-siRNA into BGC823 cells. B-RAF-siRNA significantly inhibited the expression of B-RAF gene and Bcl-2 gene in BGC823 cells by more than 90% to 100%. B-RAF-siRNA inhibited BGC823 cell prolifera-tion and induced apoptosis (P < 0.01). In conclusion, B-RAF-siRNA can effectively inhibit the expression of B-RAF gene and Bcl-2 gene, induce cell apoptosis and inhibit the proliferation of gastric cancer BGC823 cells.
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PMID:[Effect of B-RAF-specific RNA interference on gastric cancer BGC823 cell line]. 1754 20

Although some isoprenoids, such as taxans and geranylgeraniol (GGOH), have been reported to have strong anticancer activities, the effect of plaunotol, the isoprenoid extracted from the leaves of Plau-noi, on cancer has not yet been evaluated. Here, we aimed to investigate the effect of plaunotol on gastric cancer cell lines. Three gastric cancer cell lines, namely MKN-45, MKN-74 and AZ-521 were used. Plaunotol was tested at 10, 20, 30 and 40 micromol/L. Plaunotol dose-dependently inhibited the growth of all gastric cancer cells, dependent on the induction of apoptosis. Caspases-8, -9 and -3, were found to be activated in the apoptotic cells. The expression of Bax protein was increased, but Bcl-2 and Bcl-xL protein expressions were not significantly affected. Plaunotol should be a promising new antitumor agent, and since it is already available for clinical use in Japan, its anticancer properties should be confirmed in clinical trials.
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PMID:Plaunotol induces apoptosis of gastric cancer cells. 1769 Oct 55

Mounting evidence indicates that deregulation of apoptosis contributes to the development of human cancers. BAD, a proapoptotic Bcl-2 family protein, regulates the intrinsic apoptosis pathway. The aim of this study was to explore whether alterations of phospho-BAD (p-BAD) protein that antagonizes apoptosis function of BAD and mutation of BAD gene are characteristics of human gastric cancers. We analyzed expression of p-BAD in 60 gastric adenocarcinomas by immunohistochemistry. Also, we analyzed BAD gene for detection of somatic mutations by single-strand conformation polymorphism (SSCP) assay. p-BAD expression was detected well in normal gastric mucosal epithelial cells, whereas it was detected in only 51% (31 of the 60) of the cancers. There was no somatic mutation of BAD gene in the 60 gastric cancer samples. The decreased expression of p-BAD in malignant gastric epithelial cells compared to normal mucosal epithelial cells suggested that loss of p-BAD expression may play a role in gastric tumorigenesis. The data also suggest that BAD mutation may not be a direct target of inactivation in gastric tumorigenesis.
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PMID:Immunohistochemical analysis of phospho-BAD protein and mutational analysis of BAD gene in gastric carcinomas. 1769 55

Phosphatidylinositol 3-kinase/Akt pathway is an important intracellular pathway that is frequently activated in cancer cells. The role of P-AKT in multidrug resistance of gastric cancer cells and the possible underlying mechanisms are here investigated. Up-regulation of P-AKT expression could confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on AGS cells, and suppress adriamycin-induced apoptosis, along with decreased accumulation and increased releasing amount of adriamycin. P-AKT could significantly up-regulate the expression of Bcl-2, and down-regulate the expression of Bax, but not alter the expression of PTEN in gastric cancer cells. Inhibition of P-AKT expression could partially reverse P-AKT-mediated multidrug resistance and significantly up-regulate P53 expression, and down-regulate the expression of P-glycoprotein and the transcription of the multidrug resistance gene 1. Further studies of the biological functions of P-AKT may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and developing possible therapeutical strategies.
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PMID:Phospho Akt mediates multidrug resistance of gastric cancer cells through regulation of P-gp, Bcl-2 and Bax. 1772 7

Previous in vivo studies have suggested that lactobacilli can exert anti-proliferative effects on the gastric epithelium. However, few data are available on their mechanisms of action. The aim of this study was to investigate the effects of increasing concentrations of Lactobacillus rhamnosus strain GG (L. GG) homogenate on cell growth and proliferation [by 3-(4,5 di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, [(3)H]-thymidine incorporation and polyamine biosynthesis] and apoptosis processes (by Bax/Bcl-2 mRNA expression) in HGC-27 human gastric cancer cells. To verify which bacterial fraction was involved in the antiproliferative and proapoptotic effects, the cytoplasm and cell wall extracts were tested separately. HGC-27 cells were sensitive to the apoptotic induction and growth inhibition by increased concentrations of bacterial homogenate. HGC-27 cells were resistant to the bacterial cell wall fractions, whereas increasing cytoplasm fraction concentrations induced evident antiproliferative and proapoptotic actions. These data suggest that cytoplasm extracts could be responsible for L. GG action on HGC-27 cell proliferation.
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PMID:Effects of Lactobacillus rhamnosus GG on the cell growth and polyamine metabolism in HGC-27 human gastric cancer cells. 1792 9

Hypoxia induced drug resistance is a major obstacle in the development of effective cancer therapy. Our previous study revealed that hypoxia-inducible factor-1 (HIF-1), the major transcriptional factor significantly activated by hypoxia, was overexpressed in gastric vincristine-resistant cells SGC7901/vincristine (VCR) under normoxic conditions, which suggested that it was associated with drug resistance in gastric cancer cells. In the present study, a colony-forming assay revealed that hypoxia and forced HIF-1 alpha expression increased maximal -8.9-fold or -14.8-fold of IC(50) toward vincristine in gastric cancer cell lines SGC7901 and SGC7901/VCR, respectively (P < 0.01). Annexin-V/propidium iodide staining analysis revealed hypoxia or forced HIF-1 alpha expression reduced apoptosis by 24% or 18% in SGC7901 cells (P < 0.05). Flow cytometry analysis of intracellular adriamycin revealed that hypoxia and forced expression of HIF-1 alpha increased -1.79-fold or -2.36-fold of the adriamycin releasing index, respectively (P < 0.05). However, resistance acquisition subject to hypoxia in vitro and in vivo was suppressed by blocking HIF-1 alpha expression with siRNA. We further demonstrated that HIF-1 alpha overexpression showed a 1.85-fold increased expression of Bcl-2 and a 2.16-fold decreased expression of Bax, and also showed significantly induced expression of p-gp and MRP1, which indicated that HIF-1 alpha may confer hypoxia-induced drug resistance via inhibition of drug-induced apoptosis and decreases in intracellular drug accumulation.
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PMID:Hypoxia-inducible factor-1 alpha contributes to hypoxia-induced chemoresistance in gastric cancer. 1795 12

The subjects of the study were 104 patients with Helicobacter pylori (HP)-associated gastric pathology, including 30 patients with gastric ulcer (GU), 30 patients with chronic atrophic gastritis (CAG), 20 patients with CAG plus adenomatous polyps (AP), and 24 patients with gastric cancer (GC). All the subjects were examined dynamically; the comparison group consisted of 12 practically healthy people. The study revealed that GU, CAG, AP, and GC were consequent stages of gastric mucosal epithelial cell regeneration disorder which manifested by the fact that the apoptotic activity of these cells was lower than their proliferation rate, and this difference grew with time; the reflection of this was the growth of Ki-67 and Bcl-2 expression. HP eradication improved the process of cell regeneration. Epithelial cell apoptosis/proliferation ratio tended to normalize, which suggests that the processes of mucosal atrophy and metaplasia, and initial signs of gastric mucosal dysplasia in patients with HP-associated pathology may be reversible.
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PMID:[Specifics of apoptotic activity and expression of regulatory molecules (Ki-67, Bcl-2) of gastric mucosal epitheliocytes, in the process of Correa's cascade]. 1815 81

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid (PA) and choline. There are at least two PLD isozymes, PLD1 and PLD2. Genetic and pharmacological approaches implicate both PLD isozymes in a diverse range of cellular processes, including receptor signaling, membrane transport control, and actin cytoskeleton reorganization. Several recent studies reported that PLD has a role in signaling pathways that oppose apoptosis and promote cell survival in cancer. In this study, we examined the role of PLD in taxotere-induced apoptosis in stomach cell lines; normal stomach (NSC) and stomach cancer cells (SNU 484). Taxotere treatment resulted in increase of PLD activity. To confirm the role of PLD in taxotere-induced apoptosis, PLDs were transfected into SNU 484 cells. Overexpression of PLD isozymes resulted in inhibition of taxotere-induced apoptotic cell death, evidenced by decreased degradation of chromosomal DNA, and increased cell viability. Concurrently, Bcl-2 expression was upregulated, and taxotere-induced activation of procaspase 3 was inhibited after PLD's transfection. However, when PLD was selectively inhibited by specific siRNA-PLD1 or -PLD2, taxotere-induced apoptosis was exacerbated in SNU 484 cells. On top of this, PA -- the product of PLDs, also resulted in upregulation of Bcl-2 in SNU 484. Although PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of phospholipase A(2) (PLA(2)), increased Bcl-2 expression by PA was not abrogated by propranolol, an inhibitor of PA phospholyhydrolase (PAP). Taken together, PLD1 and PLD2 are closely related with Bcl-2 expression together with PLA(2), but not with PAP, during taxotere-induced apoptosis in SNU 484 cells.
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PMID:Overexpression of phospholipase D suppresses taxotere-induced cell death in stomach cancer cells. 1819 Jul 95


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