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Biochem Biophys Res Commun ; 515(1): 37-43, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31122697


miR-613 has been demonstrated to play critical roles in tumorigenesis and progression of a various type of cancers. However, its role and expression significance remain unclear in gastric cancer (GC). We detected the expression of miR-613 in 176 paired GC tissues and adjacent normal tissues, and found that miR-613 was significantly downregulated in GC tissues and its downregulation was correlated with T stage, lymph node invasion and advanced AJCC stages. Moreover, miR-613 expression could be an independent prognostic factor of GC. Biological function analysis indicated that miR-613 inhibited cell proliferation and invasion. Further analysis suggested that miR-613 inhibited Warburg effect of GC cells. Mechanically, we identified that miR-613 could directly bind to the 3'UTR of PFKFB2, thereby suppressing the expression of PFKFB2, which in turn, regulating glycolysis metabolism and cell growth. In conclusion, miR-613 served as a tumor suppressor by targeting PFKFB2, indicating that detecting miR-613 and modulation of miR-613 expression could be potential marker and clinical approach in GC patients.

Int J Oncol ; 42(4): 1417-26, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23404079


Matrine has potent antitumor activity against a broad variety of cancer cells and our previous study showed that both autophagy and apoptosis were activated during matrine-induced gastric cancer cell death. The aim of the present study was to determine the significance of autophagy in antineoplastic effects of matrine and the molecular mechanism by which matrine induces autophagy in gastric cancer cells. Western blot analysis showed that exposure of gastric cancer cells to matrine resulted in the extent of autophagy increasing in a dose- and time-dependent manner by detecting micro-tubule-associated protein 1 light chain 3 (LC3). This induction was due to activation of autophagic flux, as supported using the lysosome inhibitor, bafilomycin A1, which produced an accumulation of LC3-II. Propidium iodide staining demonstrated that matrine induced cell death in a dose-dependent manner and the autophagy inhibitor 3-methyladenine (3-MA) or bafilomycin A1 enhanced lethality of matrine against gastric cancer cells. Moreover, after pretreatment with 3-MA, some of the gastric cancer cells treated with matrine exhibited prototypical characteristics of apoptosis by transmission electron microscopy. The ability of 3-MA to increase matrine-induced apoptosis was further confirmed by Annexin V-FITC/PI staining. Also, the combination of matrine and 3-MA was more potent than matrine alone in inhibiting the proliferation of SGC-7901 cells assessed by sulphorhodamine B assay. Furthermore, administration of the pan-caspase inhibitor zVAD-fmk or autophagy inducer rapamycin decreased the matrine-induced cell death. In addition, matrine treatment did not inhibit the phosphorylation of Akt and its downstream effectors mammalian target of rapamycin (mTOR) as well as p70 ribosomal protein S6 kinase (p70S6K), although the levels of the total Akt and mTOR were decreased. These results suggest that autophagy was activated as a protective mechanism against matrine-induced apoptosis and inhibition of autophagy may be an attractive strategy for enhancing the antitumor potential of matrine in gastric cancer.

Alcaloides/farmacologia , Autofagia/efeitos dos fármacos , Quinolizinas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Adenina/análogos & derivados , Adenina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Imunoglobulina G/farmacologia , Macrolídeos/farmacologia , Melfalan/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo
Biochem Biophys Res Commun ; 419(4): 656-61, 2012 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-22382024


Hepatocellular carcinoma (HCC) is one of the most common internal malignant tumors. Glypican-3 (GPC3) is involved in the biological and molecular events in the tumorigenesis of HCC. We used RNA interference to evaluate the molecular effects of GPC3 suppression at the translational level and demonstrated for the first time that GPC3 silencing results in a significant elevation of the Bax/Bcl-2 ratio, the release of cytochrome c from mitochondria and the activation of caspase-3. The results suggest that GPC3 regulates cell proliferation by enhancing the resistance to apoptosis through the dysfunction of the Bax/Bcl-2/cytochrome c/caspase-3 signaling pathway and therefore plays a critical role in the tumorigenesis of HCC. Thus, the knockdown of GPC3 should be further investigated as an attractive novel approach for the targeted gene therapy of HCC.

Apoptose/genética , Carcinoma Hepatocelular/genética , Glipicanas/fisiologia , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/terapia , Caspase 3/metabolismo , Citocromos c/metabolismo , Inativação Gênica , Terapia Genética , Glipicanas/antagonistas & inibidores , Glipicanas/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/terapia , Interferência de RNA , Proteína X Associada a bcl-2/metabolismo
Am J Med Sci ; 343(2): 155-161, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21709535


Autophagy is an intracellular lysosome-dependent catabolic process that is indispensable for maintaining cellular homeostasis through the turnover and elimination of defective or redundant proteins and damaged or aged organelles. Recent studies suggest that autophagy may be closely associated with tumorigenesis and the response of tumor cells to chemotherapeutic drugs. This article reviews recent advances in understanding the molecular mechanisms underlying the regulation of autophagy and the role of autophagy in oncogenesis and anticancer therapy. It is paradoxical that autophagy acts as a mechanism for tumor suppression and contributes to the survival of tumors. In addition, whether autophagy in response to chemotherapies results in cell death or instead protects cancer cells from death is complicated, depending on the nature of the cancer and the drug.

Autofagia , Transformação Celular Neoplásica , Neoplasias , Animais , Apoptose , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Transformação Celular Neoplásica/efeitos da radiação , Humanos , Camundongos , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Transdução de Sinais , Enzimas de Conjugação de Ubiquitina/metabolismo
Mol Cell Biochem ; 362(1-2): 241-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22081333


In Hexi area of Gansu Province, people have a higher susceptibility of gastric cancer than people in the rest area of China. There is substantial geographic variation in the incidence of gastric cancer. In this article, the present author explored the roles of H. pylori infection and IL-10 promoter polymorphisms in development of gastric cancer in this area. A total of 304 participants were admitted to our study, and they were divided into two groups: control group and case group. Blood samples from all subjects were collected for gene extraction using DNA extraction kits. IL-10 polymorphisms were determined by SNaPshot Multiplex. To test H. pylori infection and its typing H. pylori antibody Immunoblotting Kits were used. This research suggested that environmental factor played an important role in the pathogenesis of gastric carcinoma in the area, H. pylori infection increased the risk of gastric cancer (OR = 2.612, 95% CI 1.636-4.170) and subject with H. pylori I-type positive was at significantly higher risk for progression to gastric cancer (OR = 4.712, 95% CI 2.656-8.537). For subjects with the ATA/GCC or GCC/GCC haplotype of the IL-10-1082/-819/-592 polymorphism relative to the ATA/ATA haplotype group, the risk of gastric cancer development was significantly increased. It has been demonstrated that the presence of IL-10-819 C alleles and IL-10-592 C alleles was associated with an increased risk for gastric cancer development in H. pylori-infected patients and IL-10 promoter polymorphisms and H. pylori have a synergistic effect on gastric cancer in Hexi population.

Predisposição Genética para Doença , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Interleucina-10/genética , Regiões Promotoras Genéticas , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Genótipo , Helicobacter pylori/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/microbiologia
World J Gastroenterol ; 16(37): 4738-46, 2010 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-20872977


AIM: To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557, rs4880), Helicobacter pylori (H. pylori) infection and environmental factors in gastric cancer (GC) and malignant potential of gastric precancerous lesions (GPL). METHODS: Copper-zinc superoxide dismutase (SOD1, CuZn-SOD)-G7958A (rs4998557) and manganese superoxide dismutase (SOD2, Mn-SOD)-Val16Ala (rs4880) polymorphisms were genotyped by SNaPshot multiplex polymerase chain reaction (PCR) in 145 patients with GPL (87 cases of gastric ulcer, 33 cases of gastric polyps and 25 cases of atrophic gastritis), 140 patients with GC and 147 healthy controls. H. pylori infection was detected by immunoblotting analysis. RESULTS: The SOD1-7958A allele was associated with a higher risk of gastric cancer [odds ratio (OR) = 3.01, 95% confidence intervals (95% CI): 1.83-4.95]. SOD2-16Ala/Val genotype was a risk factor for malignant potential of GPL (OR = 2.04, 95% CI: 1.19-3.49). SOD2-16Ala/- genotype increased the risk of gastric cancer (OR = 2.85, 95% CI: 1.66-4.89). SOD1-7958A/- genotype, SOD2-16Ala/- genotype, alcohol drinking, positive family history and type I H. pylori infection were associated with risk of gastric cancer, and there were additive interactions between the two genotypes and the other three risk factors. SOD2-16Ala/Val genotype and positive family history were associated with malignant potential of GPL and jointly contributed to a higher risk for malignant potential of GPL (OR = 7.71, 95% CI: 2.10-28.22). SOD1-7958A/- genotype and SOD2-16Ala/- genotype jointly contributed to a higher risk for gastric cancer (OR = 6.43, 95% CI: 3.20-12.91). CONCLUSION: SOD1-7958A/- and SOD2-16Ala/-genotypes increase the risk of gastric cancer in Chinese Han population. SOD2-16Ala/-genotype is associated with malignant potential of GPL.

Predisposição Genética para Doença , Polimorfismo Genético , Neoplasias Gástricas , Superóxido Dismutase/genética , Adulto , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Grupos Étnicos/genética , Feminino , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia