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1.
Nat Commun ; 10(1): 5230, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745089

RESUMO

The Hengduan Mountains (HDM) biodiversity hotspot exhibits exceptional alpine plant diversity. Here, we investigate factors driving intraspecific divergence within a HDM alpine species Salix brachista (Cushion willow), a common component of subnival assemblages. We produce a high-quality genome assembly for this species and characterize its genetic diversity, population structure and pattern of evolution by resequencing individuals collected across its distribution. We detect population divergence that has been shaped by a landscape of isolated sky island-like habitats displaying strong environmental heterogeneity across elevational gradients, combined with population size fluctuations that have occurred since approximately the late Miocene. These factors are likely important drivers of intraspecific divergence within Cushion willow and possibly other alpine plants with a similar distribution. Since intraspecific divergence is often the first step toward speciation, the same factors can be important contributors to the high alpine species diversity in the HDM.

2.
Toxicology ; 417: 42-53, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30769052

RESUMO

Tocotrienols (T3s) are a subgroup of vitamin E and they have been widely tested to inhibit cell growth in various tumor types. Previous studies have shown that T3s inhibit cancer cell growth by targeting multiple signaling transduction and cellular processes. However, the role of T3s in the regulation of cellular bioenergetic processes remains unclear. In this study, we found that γ-T3 interacts with mitochondrial electron transfer chain NDUFB8 (a subunit of complex I) and SDHB (a subunit of complex II) and inhibits oxidative phosphorylation (OXPHOS), and triggers the production of reactive oxygen species (ROS). In addition, we observed that γ-T3 upregulates the glycolytic capacity in cells, but it did not compensate for cellular ATP generation and decreased the ATP levels in cells. Furthermore, we performed western blots and RT-PCR to measure the mRNA and protein levels of mitochondrial electron transfer chain (ETC) proteins and complex V (ATP synthase), where the results indicated that γ-T3 specifically inhibited the levels of NDUFB8 and SDHB, whereas it had little effect on UQCRC2 (a subunit of complex III), COX4I1 (a subunit of complex IV), and ATP5F1A (a subunit of complex V). The inhibition of NDUFB8 and SDHB by γ-T3 led to the overproduction of ROS and the depletion of ATP, which may be responsible for inducing apoptosis in cancer cells. Our results suggest that mitochondrial respiration may be an effective target for anticancer treatments based on γ-T3.


Assuntos
Apoptose/efeitos dos fármacos , Cromanos/farmacologia , Complexo I de Transporte de Elétrons/antagonistas & inibidores , Fosforilação Oxidativa/efeitos dos fármacos , Succinato Desidrogenase/antagonistas & inibidores , Vitamina E/análogos & derivados , Apoptose/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Complexo I de Transporte de Elétrons/metabolismo , Humanos , Succinato Desidrogenase/metabolismo , Vitamina E/farmacologia
3.
J Agric Food Chem ; 67(1): 441-451, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30562020

RESUMO

γ-Tocotrienol (γ-T3) exhibits the activity of anticancer via regulating cell signaling pathways. Nuclear factor-κB (NF-κB), one of the crucial pro-inflammatory factors, is involved in the regulation of cell proliferation, apoptosis, invasion, and migration of tumor. In the present study, NF-κB activity inhibited by γ-T3 was investigated in gastric cancer cells. Cell proliferation, NF-κB activity, active protein phosphatase type 2A (PP2A), and ataxia-telangiectasia mutated (ATM) protein were explored using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT), methylene blue, enzyme-linked immunosorbent assay (ELISA), malachite green, luciferase, and Western blotting assays. The effects of γ-T3 on tumor growth and the expression of NF-κB and PP2A proteins were also further examined by implanting human gastric cancer cells in a BALB/c nude mouse model. The results showed that γ-T3 significantly inhibited the cell proliferation and attenuated the NF-κB activity in vitro and in vivo. γ-T3 dramatically increased PP2A activity and protein expression, which suppressed ATM phosphorylation and its translocation to the cytoplasm in gastric cancer cells. Thus, our findings may provide mechanistic insight into effects of γ-T3 on the regulation of NF-κB activity by a PP2A-dependent mechanism and suggest that PP2A may serve as a molecular target for a potential chemopreventive agent.


Assuntos
Proliferação de Células/efeitos dos fármacos , Cromanos/administração & dosagem , NF-kappa B/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Vitamina E/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/genética , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/fisiopatologia , Vitamina E/administração & dosagem
4.
Biomed Environ Sci ; 31(9): 637-644, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30369342

RESUMO

OBJECTIVE: The primary aim of the study was to compare two nutritional status evaluation tools: the Patient-Generated Subjective Global Assessment (PG-SGA) and Nutritional Risk Screening (NRS-2002). Using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30), the second aim was to provide constructive advice regarding the quality of life of patients with malignancy. METHODS: This study enrolled 312 oncology patients and assessed their nutritional status and quality of life using the PG-SGA, NRS-2002, and EORTC QLQ-C30. RESULTS: The data indicate that 6% of the cancer patients were well nourished. The SGA-A had a higher sensitivity (93.73%) but a poorer specificity (2.30%) than the NRS-2002 (69.30% and 25.00%, respectively) after comparison with albumin. There was a low negative correlation and a high similarity between the PG-SGA and NRS-2002 for evaluating nutritional status, and there was a significant difference in the median PG-SGA scores for each of the SGA classifications (P < 0.001). The SGA-C group showed the highest PG-SGA scores and lowest body mass index. The majority of the target population received 2 points for each item in our 11-item questionnaire from the EORTC QLQ-C30. CONCLUSION: The data indicate that the PG-SGA is more useful and suitable for evaluating nutritional status than the NRS-2002. Additionally, early nutrition monitoring can prevent malnutrition and improve the quality of life of cancer patients.


Assuntos
Neoplasias/fisiopatologia , Avaliação Nutricional , Estado Nutricional , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Oncol Rep ; 40(2): 999-1007, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29901169

RESUMO

γ-tocotrienol (γ-T3), a tocotrienol isoform belonging to the vitamin E family, has been revealed to exert inhibitory effects on proliferation, migration and invasion in human gastric cancer cells. However, its precise mechanism of action is still unclear and needs to be further tested. Cyclooxygenase-2 (COX-2) is well known for its key role in promoting the migration and invasion abilities of human gastric cancer cells. In light of these data, our study aimed to validate whether the inhibitory actions of γ-T3 could be achieved by downregulation of COX-2 activity in vitro. In the present study, a Cell Counting Kit-8 (CCK-8) assay was performed to observe proliferation in human gastric cancer cells (SGC-7901 and MGC-803 cells), and wound healing and Transwell chamber assays were performed to detect migration and invasion. Western blot analyses were performed to analyse the relative expression of COX-2, matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) proteins, and enzyme-linked immunosorbent assays (ELISA) were used to determine the exocrine roles of MMP-2 and MMP-9. The results revealed that γ-T3 exerted significant inhibitory effects on proliferation, migration, invasion and COX-2 protein expression, as well as on exocrine functions of MMP-2 and MMP-9 in SGC-7901 and MGC-803 cells. Therefore, our results indicated that γ-T3 exerts inhibitory effects on migration and invasion, which may be mediated through downregulation of COX-2 expression in SGC-7901 and MGC-803 cells.


Assuntos
Movimento Celular/efeitos dos fármacos , Cromanos/farmacologia , Ciclo-Oxigenase 2/genética , Regulação para Baixo/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Neoplasias Gástricas/tratamento farmacológico , Vitamina E/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Invasividade Neoplásica/genética , Neoplasias Gástricas/genética , Vitamina E/farmacologia
6.
Mol Phylogenet Evol ; 125: 93-99, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29526806

RESUMO

In the present study, we used genetic data and ecological niche modelling to explore possible historical introgressions among the species of Rodgersia (Saxifragaceae) in central-southwest China. Markedly differentiated chloroplast haplotypes were found in R. aesculifolia, R. sambucifolia and the Lijiang (LJ) population of R. pinnata, respectively, and differentiated chloroplast haplotypes within each of them showed the closest relationships with haplotypes from different species. ITS cloning did not reveal any shared ribotype between R. aesculifolia and the remaining species. Historical introgression between R. aesculifolia and R. sambucifolia (or R. pinnata) seems to be the most plausible explanation according to the geographical pattern and derivative status of putative introgressed chloroplast haplotypes, and also from morphological evidence. Introgressions were also found among R. sambucifolia, R. pinnata, and R. henricii from Yunnan. Frequent gene exchanges may have promoted the diversity of leaf shapes in this genus. Ecological niche modelling indicated that past secondary contact following range shifts during Pleistocene cold periods may have provided opportunities for ancient introgression between R. aesculifolia and adjacent species.


Assuntos
Ecossistema , Florestas , Saxifragaceae/genética , China , DNA de Cloroplastos/genética , Variação Genética , Geografia , Haplótipos/genética , Filogenia , Probabilidade , Especificidade da Espécie
7.
Ying Yong Sheng Tai Xue Bao ; 27(4): 1135-1144, 2016 Apr 22.
Artigo em Chinês | MEDLINE | ID: mdl-29732769

RESUMO

The effects of exogenous nitrogen on N2O production processes in the soils of un-restoration wetland (R0), restoration wetland since 2007 (R2007) and restoration wetland since 2002 (R2002) of the Yellow River estuary were studied, and the contributions of different processes in N2O production were determined. Results showed that the N2O production of restoration wetland soils (R2002 and R2007) with NO3--N addition was much higher than that with NH4+-N addition, but both NH4+-N and NO3--N additions demonstrated inhibition on the N2O production of soils in R0. Although the effect of NO3--N addition on the total N2O production of topsoil in R2002 was significantly higher than those in R2007, the values in R2002 and R2007 were greatly increased with increasing NO3--N addition. The denitrification and nitrifier denitrification processes in restoration wetland soils (R2002 and R2007) were greatly affected by NO3--N addition, but no significant influence on the non-biological processes of soil in R0 was observed. Although NH4+-N addition did not produce significant effects on the total N2O production of wetland soils, the nitrifier denitrification process in R0 soil, the nitrification process in R2007 soil and the non-biological process in R2002 soil were generally stimulated. In R0 and R2002 soils, the N2O produced by non-biological processes was generally eleva-ted with NH4+-N addition, while with NO3--N addition, the non-biological processes generating N2O in R0, R2002 and R2007 soils were generally inhibited, which was closely correlated with the regulation of soil pH caused by the import of exogenous nitrogen. This study found that the enrichment of NO3--N greatly enhanced the total N2O production of wetland soils and significantly altered the original contribution patterns of biological and non-biological processes to N2O production. Thus, special attention should be paid on the influences of nutrient import (particularly NO3--N enrichment) induced by ecological restoration project on N2O production of wetland soils.


Assuntos
Nitrogênio/química , Óxido Nitroso/química , Solo/química , Áreas Alagadas , China , Desnitrificação , Estuários , Nitrificação , Rios
8.
Huan Jing Ke Xue ; 35(8): 3110-9, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25338387

RESUMO

By using the method of time-space mutual substitution, the contribution of different processes in wetland soil N2O production was studied in the un-restoration wetland (R0), restoration wetland since 2007 (R2007) and restoration wetland since 2002 (R2002) of the Yellow River estuary to evaluate the effectiveness of the restoration projects. Results showed wetland soil total N2O production had a significant difference in different restoration phases, but the N2O release was the main source. The N2O production in restoration wetland was higher than that in un-restoration wetland. The N2O production wss mainly due to the nitrification and nitrifier denitrification processes, while the denitrification process had great weakening effects on N2O production, which was closely related to the physical and chemical properties of wetland soils in different restoration phases. The non-biological processes made greater contributions to N2O production and these were mainly due to that iron was reductive, while the Yellow River estuary was an area of highly active iron. Although N2O production in wetland soils was the results of biological processes combined with non-biological processes in different restoration phases, non-biological processes had larger influences and should be paid a special attention. There were different influences on wetland soil processes generating N2O between temperature and water content, indicating responses of soil microbial activities to temperature and water content were different. In addition, the N2O production contents ranged from 0.37 +/- 0.08 nmol x (kg x h) (-1) to 9.75 +/- 7.64 nmol x (kg x h) (-1) in marshes of the Yellow River estuary, which was slightly higher than those in the S. alterniflora wetland soils of the Min River estuary, but significantly lower than those in the C. malaccensis wetland soils of the Min River estuary, the grassland soils and the aerobic forest soils. We found that the long-term implements of ecological restoration project in the Yellow River estuary obviously promoted N2O production, so we should consider two factors of landscape restoration and weakening greenhouse gases in the next wetland restoration project.


Assuntos
Recuperação e Remediação Ambiental , Estuários , Óxido Nitroso/química , Solo/química , Áreas Alagadas , China , Desnitrificação , Nitrificação , Rios
9.
Arch Toxicol ; 87(10): 1797-808, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23536271

RESUMO

ß-Ionone is an end ring analog of ß-carotenoid which has been shown to possess potent anti-proliferative activity both in vitro and in vivo. To investigate the possible inhibitory effects of ß-ionone, we studied cell growth characteristics, DNA synthesis, cell cycle progression, as well as mitogen-activated protein kinases (MAPKs) pathways in the human gastric adenocarcinoma cancer cell line (SGC-7901). Our results show that cell growth and DNA synthesis were inhibited, and the cell cycle was arrested at the G0/G1 phase in a dose-dependent manner in cells treated with ß-ionone (25, 50, 100 and 200 µmol/L) for 24 h. We found that the ß-ionone significantly decreased the extracellular signal-regulated kinase protein expression and significantly increased the levels of p38 and Jun-amino-terminal kinase protein expression (P < 0.01). ß-Ionone also inhibited cell cycle-related proteins of Cdk4, Cyclin B1, D1 and increased p27 protein expression in SGC-7901 cells. These results suggested that the cell cycle arrest observed may be regulated through a MAPK pathway by transcriptional down-regulation of cell cycle proteins. These results demonstrate potent ability of ß-ionone to arrest cell cycle of SGC-7901 cells and decrease proliferation.


Assuntos
Adenocarcinoma/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Norisoprenoides/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA/biossíntese , DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Norisoprenoides/administração & dosagem , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Neoplasias Gástricas/patologia
10.
Arch Toxicol ; 87(3): 481-90, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23100158

RESUMO

ß-ionone has been shown to hold potent anti-proliferative and apoptosis induction properties in vitro and in vivo. To investigate the effects of ß-ionone on apoptosis initiation and its possible mechanisms of action, we qualified cell apoptosis, proteins related to apoptosis and a phosphatidylinositol 3-kinase (PI3K)-AKT pathway in human gastric adenocarcinoma cancer SGC-7901 cells. The results demonstrated that ß-ionone-induced apoptosis in a dose-dependent manner in SGC-7901 cells treated with ß-ionone (25, 50, 100 and 200 µmol/L) for 24 h. ß-ionone was also shown to induce the expression of cleaved-caspase-3 and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner. The significantly decreased levels of p-PI3K and p-AKT expression were observed in SGC-7901 cells after ß-ionone treatments in a time- and dose-dependent manner (P < 0.01). Thus, the apoptosis induction in SGC-7901 cells by ß-ionone may be regulated through a PI3K-AKT pathway. These results demonstrate a potential mechanism by which ß-ionone to induce apoptosis initiation in SGC-7901 cells.


Assuntos
Adenocarcinoma/enzimologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Norisoprenoides/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/enzimologia , Adenocarcinoma/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Forma do Núcleo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Gástricas/patologia , Fatores de Tempo
11.
Exp Mol Pathol ; 95(3): 350-56, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24422232

RESUMO

OBJECTIVE: Cancer-associated fibroblasts (CAFs) are one of the most important components of tumor microenvironment. CAFs are believed to play an important role in tumor invasion and metastasis. Recently, fibroblast activation protein (FAP), a type II integral membrane glycoprotein belonging to the serine protease family, has emerged as a specific marker of CAFs. FAP was overexpressed in stromal fibroblasts of solid malignancies, however, the role of FAP on the process of invasion and metastasis of gastric carcinomas is still unknown. METHODS: Expression of FAP level was detected by immunohistochemistry in 60 gastric cancer surgical specimens (28 with omentum metastasis and 32 without), 20 normal human gastric tissues and omentum of 10 nonneoplastic gastric diseases. Fibroblasts were isolated from patient's tissues in the distal normal zones and tumor zones respectively, which were correspondingly designated as normal zone fibroblasts (NFs) and cancer-associated fibroblasts (CAFs). To explore the effects of FAP on NFs or CAFs, fibroblasts were co-cultured with human gastric cancer cell line MGC-803 cells. The ability of invasion and migration of MGC-803 cells was evaluated after transfecting FAP siRNA into CAFs of gastric carcinomas. RESULTS: We investigated the level of expression of FAP in surgical specimens, and found overexpressed in CAFs and non-expressed in NFs. Expression of FAP level in CAFs is significantly associated with Lauren classification,the degree of differentiation, depth of tumor invasion and TNM stage, but it is not correlated to age and gender in gastric carcinoma patients. There was positive correlation between the FAP level with metastasis to the omentum(p < 0.05, R(2) = 0.2736, p < 0.05, R(2) = 0.1479). In addition, the invasion and migration abilities of MGC-803 cells were significantly increased when cells were co-cultured with CAFs. On the other hand, invasion and migration abilities were significantly decreased by 46.9 and 50.3%, respectively, after knocking down FAP in CAFs.Further, NFs did not have appreciable effect on the invasion and migration of MGC-803 cells. CONCLUSIONS: Our findings showed that FAP was overexpressed in CAFs of gastric carcinomas, and siRNA-mediated knock down of FAP significantly suppressed invasion and migration of MGC-803 cells. FAP may be an important regulator in the invasion and migration of gastric cancer and may provide a novel therapeutic target in gastric carcinomas.


Assuntos
Movimento Celular , Fibroblastos/patologia , Gelatinases/metabolismo , Proteínas de Membrana/metabolismo , Omento/patologia , Serina Endopeptidases/metabolismo , Neoplasias Gástricas/patologia , Estômago/patologia , Western Blotting , Adesão Celular , Proliferação de Células , Células Cultivadas , Feminino , Fibroblastos/metabolismo , Mucosa Gástrica/metabolismo , Gelatinases/antagonistas & inibidores , Gelatinases/genética , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Omento/metabolismo , RNA Interferente Pequeno/genética , Serina Endopeptidases/genética , Neoplasias Gástricas/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia
12.
Huan Jing Ke Xue ; 34(11): 4411-9, 2013 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-24455953

RESUMO

The spatial distribution characteristics of Fe and Mn contents in soils of nine different vegetation communities, located in the new-born marshes of the northern Yellow River estuary, were studied in May 2009. The results showed that the horizontal distributions of Fe and Mn contents showed an increasing tendency from Sparganiaceae-Potentilla supina marsh to bare flat. The vertical distribution characteristics of Fe and Mn contents in different marsh soils fluctuated significantly with the vegetation succession. The soil parent materials determined the Fe, Mn contents in the new-born marshes, and seawater, vegetations and soil fine particle also had important influences on their contents. Further analysis showed that Fe contents had significant positive correlation with Mn contents (P < 0.01). Fe, Mn contents also showed significant correlations with silt, clay, TN, NO3(-) -N and organic matter (P < 0.05), indicating that Fe and Mn had close relationships with nitrogen, and the contents of soil fine particles and organic matter were the dominant factors affecting the distribution of Fe and Mn in soils. In addition, the Fe contents ranged from 16.49 g x kg(-1) to 33.11 g x kg(-1) and the average was 22.54 g x kg(-1), which was close to the Fe contents in the tidal marshes of north Jiangsu, the Loess Plateau and the China soil background value, but slightly lower than those in the marshes of the Yangtse River estuary, the mangrove swamps and inland lake wetland. The Mn contents ranged from 305.87 mg x kg(-1) to 711.39 mg x kg(-1) and the average was 451.09 mg x kg(-1), which was lower than the Mn contents in the Loess Plateau and the China soil background value. Hydrology and Water Resources Survey Bureau of the Yellow River Estuary, Dongying 257091, China)


Assuntos
Ferro/análise , Manganês/análise , Rios/química , Áreas Alagadas , China , Estuários , Nitrogênio/química , Água do Mar/química , Solo/química
13.
J Clin Pathol ; 65(10): 888-95, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22844068

RESUMO

AIMS: Interface zone fibroblasts (INFs) are very important in the progression and metastasis of tumours but their effect on the invasion and migration of gastric cancer cells is still unclear. METHODS: Primary fibroblasts were isolated from the distal normal zone (normal zone fibroblasts, NFs), interface zone (INFs) and tumour zone (cancer-associated fibroblasts, CAFs) of 60 human gastric carcinoma tissue samples. The crosstalk between these fibroblasts and human gastric cancer MGC-803 cells was evaluated using an indirect co-culture model in vitro. RESULTS: A high level of fibroblast activation protein (FAP) in the invasion front of gastric cancer was found in the gastric cancer tissue samples and no FAP expression was found in 20 normal gastric tissue samples by immunohistochemistry. High FAP expression was associated with Lauren classification, degree of differentiation, tumour node metastasis stage and depth of tumour invasion (p<0.05 or p<0.01). INFs promoted invasion and migration of MGC-803 cells. The number of invasions in INFs, CAFs and NFs were 120.10±27.53 (95% CI 102.12 to 138.10), 63.00±14.80 (95% CI 53.33 to 72.67) and 14.22±6.20 (95% CI 10.17 to 18.27), respectively; the number of invasions in INFs were 8.45-fold and 1.89-fold higher than those in NFs and CAFs, respectively (p<0.05). The number of migrations in INFs, CAFs and NFs were 118.00±16.83 (95% CI 107.00 to 129.00), 61.00±16.36 (95% CI 50.31 to 71.69) and 24.00±11.52 (95% CI 16.47 to 31.53), respectively; the number of migration in INFs were 4.91-fold and 1.92-fold higher than those in NFs and CAFs, respectively (p<0.05). INFs also significantly promoted cell proliferation and inhibited apoptosis in MGC-803 cells compared with NFs and CAFs (p<0.05). CONCLUSIONS: These findings indicate that INFs exhibit a more robust biological modulatory activity than CAFs and NFs. INFs may be a key factor leading to tumour progression and metastasis and may be of use as a tool for post-treatment surveillance.


Assuntos
Adenocarcinoma/patologia , Fibroblastos/fisiologia , Neoplasias Gástricas/patologia , Adenocarcinoma/metabolismo , Adulto , Idoso , Apoptose/fisiologia , Comunicação Celular/fisiologia , Movimento Celular , Proliferação de Células , Fibroblastos/metabolismo , Fibroblastos/patologia , Gelatinases/metabolismo , Humanos , Imuno-Histoquímica , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Serina Endopeptidases/metabolismo , Neoplasias Gástricas/metabolismo , Adulto Jovem
14.
Huan Jing Ke Xue ; 33(2): 565-73, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22509598

RESUMO

The characteristics of methane (CH4) fluxes from tidal wetlands of the Yellow River estuary were observed in situ with static-chamber and GC methods in September and October 2009, and the key factors affecting CH4 fluxes were discussed. From the aspect of space, the CH4 flux ranges in high tidal wetland, middle tidal wetland, low tidal wetland, bare flat are - 0.206-1.264, -0.197-0.431, -0.125-0.659 and -0.742-1.767 mg x (m2 x h)(-1), the day average fluxes are 0.089, 0.038, 0.197 and 0.169 mg x (m2 x h)(-1), respectively, indicating that the tidal wetlands are the sources of CH4 and the source function of CH4 differed among the four study sites, in the order of low tidal wetland > bare flat > high tidal wetland > middle tidal wetland. From the aspect of time, the ranges of CH4 fluxes from the tidal wetland ecosystems are -0.444-1.767 and - 0.742- 1.264 mg x (m2 x h)(-1), and the day average fluxes are 0.218 and 0.028 mg x (m2 x h)(-1) in September and October, respectively. The CH4 fluxes in each tidal wetland in September are higher than those in October except that the high tidal wetland acts as weak sink in September. Further studies indicate that the changes of environmental factors in the Yellow River estuary are complicated, and the CH4 fluxes are affected by multiple factors. The differences of CH4 fluxes characteristics among different tidal wetlands in autumn are probably related to temperature (especially atmospheric temperature) and vegetation growth status, while the effects of water or salinity condition and tide status on the CH4 flux characteristics might not be ignored.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Metano/análise , Poluentes Químicos da Água/análise , Áreas Alagadas , China , Oceanos e Mares , Rios , Estações do Ano , Ondas de Maré
15.
J Nutr Biochem ; 22(12): 1127-36, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21292465

RESUMO

Antiangiogenic therapy mediated by food components is an established strategy for cancer chemoprevention. Growth factors play critical roles in tumor angiogenesis. A conditioned medium containing growth factors from human gastric adenocarcinoma SGC-7901 cell conditioned medium was used as an angiogenic stimulus in this study. The purpose of this study was to evaluate the inhibitory effect and possible mechanism of γ-tocotrienol on tumor angiogenesis. The results showed that γ-tocotrienol (10-40 µmol/L) significantly suppressed proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) induced by SGC-7901 cell conditioned medium in a dose-dependent manner. γ-Tocotrienol (800-1200 µg/egg) also inhibited new blood vessel formation on the growing chick embryo chorioallantoic membrane in a dose-dependent manner. Moreover, the inhibitory effects of γ-tocotrienol on HUVECs were correlated with inducing the apoptosis and arresting cell cycle at the G(0)/G(1) phase at a dose of 40 µmol/L γ-tocotrienol. In addition, γ-tocotrienol inhibited angiogenesis in HUVECs by down-regulation of ß-catenin, cyclin D1, CD44, phospho-VEGFR-2 and MMP-9. The antiangiogenic effects of γ-tocotrienol on HUVECs may be attributable to regulation of Wnt signaling by decreasing ß-catenin expression. Thus, our results suggest that γ-tocotrienol has a potential chemopreventive agent via antiangiogenesis.


Assuntos
Inibidores da Angiogênese/farmacologia , Cromanos/farmacologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Neovascularização Patológica/patologia , Neovascularização Patológica/prevenção & controle , Vitamina E/análogos & derivados , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimioprevenção , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Cromanos/uso terapêutico , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Microscopia Eletrônica de Transmissão , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Neovascularização Patológica/metabolismo , Transdução de Sinais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Vitamina E/farmacologia , Vitamina E/uso terapêutico , beta Catenina/genética , beta Catenina/metabolismo
16.
Cancer Biother Radiopharm ; 25(5): 529-37, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20950152

RESUMO

The ß-catenin gene is a critical component of Wnt signaling pathway. Aberrant activation of Wnt/ß-catenin signaling and subsequent upregulation of ß-catenin is related to enhancing cell proliferation and developing colon polyps and colon cancer. In the present study, the effect of ß-catenin knockdown on the growth and survival of the human colon cancer cell line HT-29 was investigated in vitro. The effect of knockdown of ß-catenin on cell proliferation was investigated by MTT assay and colony formation. The cell cycle distribution was investigated by flow cytometry. Apoptosis was measured by nuclear staining and flow cytometry. The change of ß-catenin and related proteins were determined by western blotting and immunofluorescence. The results showed that small interfering RNA directed against ß-catenin markedly inhibited the expression and nuclear translocation of ß-catenin and decreased the expression of known target genes such as cyclin D1 and c-myc; HT-29 cell proliferation was inhibited as indicated by growth reduction, cell cycle arrest in G0/G1 phase, and induction of apoptosis; and the inhibition of cell growth may be associated with switching off cyclin D1 and c-myc expression by small interfering RNA targeted against ß-catenin in colon cancer HT-29 cells.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , RNA Interferente Pequeno/genética , beta Catenina/genética , beta Catenina/metabolismo , Apoptose , Ciclo Celular , Proliferação de Células , Neoplasias do Colo/metabolismo , Genes bcl-1 , Genes myc , Células HT29 , Humanos , Interferência de RNA , Transdução de Sinais , Transfecção , Proteínas Wnt/genética , Proteínas Wnt/metabolismo
17.
Toxicology ; 274(1-3): 27-33, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20452389

RESUMO

Hypoxia is a common characteristic feature of solid tumors, and carcinoma cells are known to secrete many growth factors. These growth factors, such as vascular endothelial growth factor (VEGF), play a major role in the regulation of tumor angiogenesis and metastasis. In this study, the effect of gamma-tocotrienol, a natural product commonly found in palm oil and rice bran, on the accumulation of HIF-1alpha protein and the paracrine secretion of VEGF in human gastric adenocarcinoma SGC-7901 cell line induced by cobalt(II) chloride (as a hypoxia mimic) was investigated. These results showed that cobalt(II) chloride induced the high expression of VEGF in SGC-7901 cells at dose of 150 micromol/L for 24h. Both basal level and cobalt(II) chloride-induced HIF-1alpha protein accumulation and VEGF paracrine secretion were inhibited in SGC-7901 cells treated with gamma-tocotrienol at 60 micromol/L treatment for 24 h. U0126, a MEK1/2 inhibitor, decreased the expression of HIF-1alpha protein and the paracrine secretion of VEGF under normoxic and hypoxic conditions. In this study, gamma-tocotrienol also significantly inhibited the hypoxia-stimulated expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). The mechanism seems to involve in inhibiting hypoxia-mediated activation of p-ERK1/2, it leads to a marked decrease in hypoxia-induced HIF-1alpha protein accumulation and VEGF secretion. These data suggest that HIF-1alpha/VEGF could be a promising target for gamma-tocotrienol in an effective method of chemoprevention and chemotherapy in human gastric cancer.


Assuntos
Proteínas/metabolismo , Neoplasias Gástricas/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adenocarcinoma , Linhagem Celular , Cromanos , Cobalto/farmacologia , Guanilato Ciclase , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/farmacologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/farmacologia , Neovascularização Patológica , Fosforilação , Proteínas/farmacologia , Receptores Citoplasmáticos e Nucleares , Transdução de Sinais/efeitos dos fármacos , Guanilil Ciclase Solúvel , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/patologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/farmacologia , Vitamina E/análogos & derivados
18.
Nutr Cancer ; 62(1): 58-65, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20043260

RESUMO

Recent chemopreventive studies from our group showed that dietary beta -ionone inhibited 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis by the inhibition of cell proliferation and apoptosis initiation. In this study, we examined the chemopreventive effects of varied doses of dietary beta -ionone on the development and growth of DMBA-induced rat mammary tumors as well as plasma antioxidant status. beta -ionone treatment groups were given 9, 18, and 36 mmol/kg in the AIN76A diet starting 2 wk prior to DMBA administration and continuing for the 24 wk. Results showed that tumor incidence was dose dependently reduced by 35.4, 68.3, and 87.8%, respectively, compared to the positive control. Tumor sizes were dose dependently smaller, and tumor weight was less in each group, each rat, and each tumor compared to the positive control (P < 0.05). A significant decrease in lipid peroxidation was observed in the tumor-induced rats treated with dietary beta -ionone, whereas the plasma activities of antioxidant enzymes such as glutathione peroxidase, glutathione reductase, superoxide dismutase, and the nonenzymatic antioxidant glutathione were increased in the beta -ionone treated rats when compared to control. The levels of catalase and lactate dehydrogenase were remarkably decreased in the beta -ionone treated groups compared to the positive control group. These results suggest that dietary beta -ionone has biologically relevant antioxidant activity and plays a chemopreventive role against DMBA induced mammary gland tumors.


Assuntos
Anticarcinógenos/administração & dosagem , Antioxidantes/análise , Dieta , Neoplasias Mamárias Experimentais/prevenção & controle , Norisoprenoides/administração & dosagem , 9,10-Dimetil-1,2-benzantraceno , Animais , Carcinógenos , Catalase/sangue , Feminino , Glutationa/sangue , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , L-Lactato Desidrogenase/sangue , Peroxidação de Lipídeos , Neoplasias Mamárias Experimentais/sangue , Neoplasias Mamárias Experimentais/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue
19.
J Nutr Biochem ; 21(3): 206-13, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19195866

RESUMO

Natural vitamin E is a mixture of two classes of compounds, tocopherols and tocotrienols. Recent research has revealed that tocotrienols, especially gamma-tocotrienol, exhibit not only the same antioxidant ability as tocopherols, but also remarkable anticancer capacity in cancer cell lines. In this study, the invasion and metastatic capacities of gastric adenocarcinoma SGC-7901 cells and the correlation with antimetastasis mechanisms induced by gamma-tocotrienol were explored. The results showed the inhibitory effects of gamma-tocotrienol at doses of 15, 30, 45 and 60 mumol/L for 48 h on cell migration and cell matrigel invasion; activities of matrix metalloproteinase (MMPs) increased in SGC-7901 cells when compared to the control group (P<.05 or P<.01). An increasing trend in the chemotactic responses to fibronectin (FN) in SGC-7901 cells was found in the gamma-tocotrienol treatments. SGC-7901 cell attachment decreased in the gamma-tocotrienol-treated groups in comparison with the control group (P<.01). The mRNA expressions of MMP-2 and MMP-9 showed that gamma-tocotrienol significantly reduced the matrigel invasion capability through down-regulation of the mRNA expressions of MMP-2 and MMP-9 (P<.01), and up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in SGC-7901 cells by treatment with gamma-tocotrienol for 48 h (P<.05). gamma-Tocotrienol also significantly increased the mRNA expression of nm23-H1 in SGC-7901 cells (P<.01). These findings suggest a potential mechanism of gamma-tocotrienol-mediated antitumor metastasis activity and indicate the role of vitamin E as potential chemopreventative agents against gastric cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Cromanos/farmacologia , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica/prevenção & controle , Neoplasias Gástricas/tratamento farmacológico , Vitamina E/análogos & derivados , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiotaxia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Nucleosídeo NM23 Difosfato Quinases/genética , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Fatores de Tempo , Inibidores Teciduais de Metaloproteinases/genética , Inibidores Teciduais de Metaloproteinases/metabolismo , Vitamina E/farmacologia
20.
Nutrition ; 25(5): 555-66, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19121919

RESUMO

OBJECTIVE: gamma-Tocotrienol is a major component of the tocotrienol-rich fraction of palm oil, but there is limited evidence that it has antitumor activity. In particular, the effects of gamma-tocotrienol on human colon carcinoma cells have not been reported. To investigate the chemopreventive effects of gamma-tocotrienol on colon cancer, we examined its capacity to inhibit proliferation and induce apoptosis in HT-29 cells and explored the mechanism underlying these effects. METHODS: We cultured HT-29 cells in the presence of gamma-tocotrienol. The effect of gamma-tocotrienol on cell proliferation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, mitotic index, and colony formation. The cell-cycle distribution was investigated by flow cytometry. We measured apoptosis by nuclear staining, transmission electron microscopy, and DNA fragmentation. Apoptosis-related proteins and the nuclear factor-kappaB p65 protein were determined by western blotting and immunofluorescence. RESULTS: gamma-Tocotrienol inhibited cell growth and arrested HT-29 cells in G(0)/G(1) phase. The 50% inhibitory concentration was 31.7 micromol/L (48 h). gamma-Tocotrienol-induced apoptosis in HT-29 cells was accompanied by downregulation of Bcl-2, upregulation of Bax, and activation of caspase-3. Furthermore, we found that gamma-tocotrienol reduced the expression level of total nuclear factor-kappaB p65 protein and inhibited its nuclear translocation. CONCLUSION: The results indicated that gamma-tocotrienol inhibits cell proliferation and induces apoptosis in HT-29 cells in a time- and dose-dependent manner, and that this process is accompanied by cell-cycle arrest at G(0)/G(1), an increased Bax/Bcl-2 ratio, and activation of caspase-3. Our data also indicated that nuclear factor-kappaB p65 protein may be involved in these effects.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromanos/uso terapêutico , Fator de Transcrição RelA/metabolismo , Vitamina E/análogos & derivados , Anticarcinógenos/farmacologia , Anticarcinógenos/uso terapêutico , Western Blotting , Caspase 3/metabolismo , Cromanos/farmacologia , Neoplasias do Colo/prevenção & controle , Fragmentação do DNA , Relação Dose-Resposta a Droga , Ativação Enzimática , Fase G1/efeitos dos fármacos , Células HT29 , Humanos , Concentração Inibidora 50 , Índice Mitótico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Fator de Transcrição RelA/efeitos dos fármacos , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Proteína X Associada a bcl-2/metabolismo
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