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1.
Chemosphere ; 238: 124602, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545211

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been known to exhibit neurotoxicity in rats; however, the underlying mechanism remains unknown and there is no available intervention. In this study, we aimed to investigate the role of oxidative and nitrosative stress in the neurotoxicity in the cerebral cortex and primary neurons in rats following the BDE-153 treatment. Compared to the untreated group, BDE-153 treatment significantly induced the neurotoxic effects in rats, as manifested by the increased lactate dehydrogenase (LDH) activities and cell apoptosis rates, and the decreased neurotrophic factor contents and cholinergic enzyme activities in rats' cerebral cortices and primary neurons. When compared to the untreated group, the oxidative and nitrosative stress had occurred in the cerebral cortex or primary neurons in rats following the BDE-153 treatment, as manifested by the increments in levels of reactive oxygenspecies (ROS), malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) mRNA and protein expressions, along with the decline in levels of superoxide dismutase (SOD) activity, glutathione (GSH) content, and peroxiredoxin I (Prx I) and Prx II mRNA and protein expressions. In addition, the ROS scavenger N-acetyl-l-cysteine (NAC) or NO scavenger NG-Nitro-l-arginine (L-NNA) significantly rescued the LDH leakage and cell survival, reversed the neurotrophin contents and cholinergic enzymes, mainly via regaining balance between oxidation/nitrosation and antioxidation. Overall, our findings suggested that oxidative and nitrosative stresses are involved in the neurotoxicity induced by BDE-153, and that the antioxidation is a potential targeted intervention.


Assuntos
Córtex Cerebral/patologia , Éteres Difenil Halogenados/toxicidade , Síndromes Neurotóxicas/patologia , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Acetilcisteína/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Glutationa/metabolismo , Éteres Difenil Halogenados/metabolismo , Masculino , Malondialdeído/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Neurotrofina 3/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Estresse Nitrosativo/fisiologia , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
2.
Int J Hypertens ; 2019: 8268573, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316827

RESUMO

Objective: To estimate the additive interaction of body mass index (BMI) and family history of hypertension (FHH) on hypertension and explore whether the interaction could be influenced by behavioural risk factors. Methods: The cross-sectional data on 5791 participants were from the China National Health Survey in Gansu province in 2016. We assessed the additive interaction by calculating the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (SI). Results: ORs for hypertension were highest in Han (13.52, 95% CI: 9.45 to 19.34) and Yugur (13.85, 95% CI: 8.48 to 22.63) with the combination of obesity and FHH. The interaction of BMI and FHH was significant in Han people, with the RERI, AP, and SI and their 95% CIs being 2.48 (1.13 to 3.82), 0.33 (0.19 to 0.47), and 1.61 (1.26 to 2.07) for overweight and FHH and 6.32 (1.91 to 10.73), 0.47 (0.27 to 0.67), and 2.02 (1.33 to 3.07) for obesity and FHH, respectively. The interaction of BMI and FHH was not significant in Yugur people. Adjustment for behavioural risk factors had little influence on the interactions, and risks of hypertension remained increased. Conclusions: BMI and FHH were associated with hypertension, and the interaction of BMI and FHH on hypertension was significant in Han but not in Yugur people. Behavioural risk factors had little influence on the associations and interactions. The exacerbation of hypertension risks by overweight or obesity in hypertension families deserves attention in weight control and community care.

3.
Food Funct ; 10(5): 2906-2913, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31070650

RESUMO

Dysfunction of the intestinal epithelial barrier plays an important role in the pathogenesis of several intestinal diseases, including celiac disease, inflammatory bowel disease, and irritable bowel syndrome. The present research was carried out to investigate the protective effect of total polysaccharides of adlay bran (TPA) on TNF-α-evoked epithelial barrier dysfunction in Caco-2 cells. Caco-2 cells were treated with or without TPA in the absence or presence of TNF-α, and transepithelial electrical resistance (TEER) and Phenol Red flux were assayed to evaluate the intestinal epithelial barrier function. The results indicated that TPA suppressed the TNF-α-induced release of pro-inflammatory factors. Furthermore, TPA obviously assuaged both the increased paracellular permeability and the decrease of TEER in TNF-α-challenged Caco-2 cells. Furthermore, TPA obviously assuaged TNF-α-evoked up-regulation of IL-8 and IL-6 expression, down-regulation of occludin and ZO-3 expression, and markedly suppressed the activation and protein expression of NF-κB p65. Our results indicated that TPA assuages the TNF-α-evoked dysfunction of the intestinal epithelial barrier by inhibiting the NF-κB p65-mediated inflammatory response.


Assuntos
Coix/química , Mucosa Intestinal/imunologia , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/imunologia , Células CACO-2 , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Mucosa Intestinal/efeitos dos fármacos , Ocludina/genética , Ocludina/imunologia , Fosforilação , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/imunologia , Fator de Necrose Tumoral alfa/genética
4.
Medicine (Baltimore) ; 98(19): e15603, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083251

RESUMO

BACKGROUND: Many studies explored the prognostic and clinicopathological significance of pretreatment serum Gamma-Glutamyltransferase (GGT) level in hepatocellular carcinoma (HCC). However, there are inconsistent results in the prognostic and clinicopathological significance of pretreatment serum GGT level in HCC. Thus, we conducted this meta-analysis to comprehensively assess the prognostic and clinicopathological significance of pretreatment serum GGT level in HCC patients. METHODS: We systematically searched PubMed, EMBASE and Web of Science for relevant studies (up to June 14, 2018). The estimated hazard ratios (HRs) were used to assess the association between pretreatment serum GGT level and survival in HCC patients. The estimated odds ratios (ORs) were applied to evaluate the correlation between pretreatment serum GGT and clinicopathological features in HCC. RESULTS: Our results showed that high pretreatment serum GGT level was significantly correlated with poor overall survival (OS) (HR = 1.70, 95% CI: 1.54-1.87; P < .01) and disease-free survival/relapse-free survival (DFS/RFS) (HR = 1.56, 95% CI: 1.42-1.71; P < .01). Additionally, our results also revealed that there was a close correlation between GGT level and several clinicopathological features in HCC patients, including vascular invasion, tumor size, tumor number and Alpha-fetoprotein (AFP) level. CONCLUSIONS: This meta-analysis shows that high pretreatment serum GGT level is significantly correlated with poor survival and unfavorable clinicopathological features in HCC patients, suggesting that pretreatment serum GGT may be an economical and effective prognostic biomarker for HCC patients. However, more high-quality studies are still warranted to further validate our findings, considering there are several limitations in this meta-analysis.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , gama-Glutamiltransferase/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/enzimologia , Humanos , Neoplasias Hepáticas/enzimologia , Prognóstico
5.
Toxicol Lett ; 311: 37-48, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31029751

RESUMO

Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons, however, the roles of mitochondria and endoplasmic reticulum (ER) remain unclear in the BDE-153-induced neuronal apoptosis. To this purpose, we observed the mitochondria and ER ultrastructure changes in the neuronal apoptosis in rats following BDE-153 treatment, detected the mitochondrial membrane potential (MMP), Ca2+-Mg2+-ATP enzyme activity, and the changes of mitochondria and ER apoptosis related molecules in rat cerebral cortex and in primary neurons following BDE-153 treatment. Results showed that compared to the control group, neuronal apoptosis was significantly increased in a dose-dependent manner in rat cerebral cortex and in primary neurons following BDE-153 treatment. In comparison with control, BDE-153 treatment induced remarkable ultrastructural changes in ER rather than in mitochondria, and the severity of ER damage was worse with the increasing BDE-153 dose. Meanwhile, ER apoptosis related molecules including caspase-12 (at mRNA level), cleaved caspase-12 (at protein level), and Tmem132a (at mRNA and protein levels) were significantly increased in the cerebral cortex in rats following BDE-153 treatment, while procaspase-12 protein was significantly decreased, comparing with control. In contrast, mitochondria apoptosis related molecules (MMP, Ca2+-Mg2+-ATP enzyme activity, cyt-C protein, caspase-3, 8, 9 mRNA, caspase-8, 9 enzyme activities) did not significantly changed in the cerebral cortex of rats or in primary neurons following BDE-153 treatment, except for the elevated caspase-3 mRNA and enzyme activity. Therefore, we conclude that BDE-153 induced neuronal apoptosis was dependent on p53, and mediated more by ER than mitochondria in the cerebral cortex of rats and in primary neurons. The findings suggest that ER is a potential sensitive target of BDE-153 neurotoxicity, providing a scientific evidence for the mechanism and intervention study on PBDE's neurotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Degeneração Neural , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Bifenil Polibromatos/toxicidade , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/ultraestrutura , Relação Dose-Resposta a Droga , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/ultraestrutura , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Neurônios/metabolismo , Neurônios/ultraestrutura , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
Toxicol Lett ; 277: 41-53, 2017 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-28559121

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been demonstrated to induce neurotoxicity in experimental rats and mice, with neuronal apoptosis as one of the major mechanisms, however, the mechanisms underlying PBDEs-induced neuronal apoptosis remain unclear. In this study, we aimed to investigate the role of calpain/p35-p25/Cdk5 pathway in BDE-153-induced neuronal apoptosis in the hippocampus and primary neurons in rats. Results showed that compared to the controls, neuronal apoptosis was significantly increased in vivo and ex vivo, as manifested by the increased hippocampus TUNEL-positive cell rates, apoptotic neurons in Hoechst and AO/EB staining, and the increased LDH activity and percentage of Annexin V-positive cells in rat hippocampus and primary neurons. Calpain activity was significantly increased in all the BDE-153-treated groups in vivo and ex vivo when compared to non-treatment controls. In addition, we showed that calpain-2 accounted for the calpain activation instead of calpain-1, as demonstrated by the up-regulated mRNA and protein expressions in calpain-2 but not calpain-1. Activated calpain truncated p35 into p25, which resulted in the p25/Cdk5 formation and activation. Calpain inhibitor PD150606 or p25/Cdk5 inhibitor Roscovitine relieved neuronal apoptosis mainly via inhibiting the p25/Cdk5 activation. Overall, the findings suggested that calpain-2/p35-p25/Cdk5 pathway was involved in BDE-153-induced neuronal apoptosis, which provides novel insight into the mechanisms of PBDE neurotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Calpaína/metabolismo , Quinase 5 Dependente de Ciclina/metabolismo , Hipocampo/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Bifenil Polibromatos/toxicidade , Animais , Calpaína/antagonistas & inibidores , Calpaína/genética , Células Cultivadas , Quinase 5 Dependente de Ciclina/genética , Inibidores de Cisteína Proteinase/farmacologia , Citoproteção , Relação Dose-Resposta a Droga , Hipocampo/enzimologia , Hipocampo/patologia , Masculino , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Neurônios/enzimologia , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/enzimologia , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/patologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
7.
MAbs ; 5(6): 882-95, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23995618

RESUMO

While myriad molecular formats for bispecific antibodies have been examined to date, the simplest structures are often based on the scFv. Issues with stability and manufacturability in scFv-based bispecific molecules, however, have been a significant hindrance to their development, particularly for high-concentration, stable formulations that allow subcutaneous delivery. Our aim was to generate a tetravalent bispecific molecule targeting two inflammatory mediators for synergistic immune modulation. We focused on an scFv-Fc-scFv format, with a flexible (A4T)3 linker coupling an additional scFv to the C-terminus of an scFv-Fc. While one of the lead scFvs isolated directly from a naïve library was well-behaved and sufficiently potent, the parental anti-CXCL13 scFv 3B4 required optimization for affinity, stability, and cynomolgus ortholog cross-reactivity. To achieve this, we eschewed framework-based stabilizing mutations in favor of complementarity-determining region (CDR) mutagenesis and re-selection for simultaneous improvements in both affinity and thermal stability. Phage-displayed 3B4 CDR-mutant libraries were used in an aggressive "hammer-hug" selection strategy that incorporated thermal challenge, functional, and biophysical screening. This approach identified leads with improved stability and>18-fold, and 4,100-fold higher affinity for both human and cynomolgus CXCL13, respectively. Improvements were exclusively mediated through only 4 mutations in VL-CDR3. Lead scFvs were reformatted into scFv-Fc-scFvs and their biophysical properties ranked. Our final candidate could be formulated in a standard biopharmaceutical platform buffer at 100 mg/ml with<2% high molecular weight species present after 7 weeks at 4 °C and viscosity<15 cP. This workflow has facilitated the identification of a truly manufacturable scFv-based bispecific therapeutic suitable for subcutaneous administration.


Assuntos
Anticorpos Biespecíficos/genética , Regiões Determinantes de Complementaridade/genética , Engenharia de Proteínas , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/metabolismo , Animais , Bacteriófagos/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Injeções Subcutâneas , Biblioteca de Peptídeos , Estabilidade Proteica , Ratos , Anticorpos de Cadeia Única/genética , Temperatura Ambiente
8.
Artigo em Chinês | MEDLINE | ID: mdl-24053918

RESUMO

OBJECTIVE: To investigate the effects of polybrominated diphenyl ether-153 (BDE-153) exposure during lactation period on the calcium ion (Ca(2+)) concentration and calcium-activated enzyme levels in cerebral cortical cells among adult rats and to provide a scientific basis for the study on the developmental neurotoxicity of BDE-153. METHODS: Forty newborn male rats were randomly and equally divided into four groups according to their body weights and litters: 1, 5, and 10 mg/kg BDE-153 groups and olive oil solvent control group. On postnatal day 10 (PND 10), the BDE-153 groups were administrated BDE-153 (0.1 ml/10 g body weight) by intraperitoneal injection, while the olive oil solvent control group was given an equal volume of olive oil. Two months later, these rats were decapitated, and the cerebral cortex was separated quickly on an ice-cold dish. The Ca(2+) concentration in cerebral cortical cells was measured by flow cytometry. The activities of calcineurin (CaN) and Ca(2+)-Mg(2+)-ATP enzyme were determined by colorimetric method. The mRNA and protein expression of calpain-1 and calpain-2 was measured by real-time quantitative PCR and Western blot. RESULTS: The mean fluorescence intensities of intracellular Ca(2+) in control group and 1, 5, and 10 mg/kg BDE-153 groups were 10.83, 1.48, 1.93, and 0.62, respectively; the 1, 5, and 10 mg/kg BDE-153 groups had significantly lower intercellular Ca(2+) concentrations than the control group (P < 0.05). The activities of CaN and Ca(2+)-Mg(2+)-ATP enzyme and mRNA and protein expression of calpain-1 showed no significant differences between the 1, 5, and 10 mg/kg BDE-153 groups and control group (P > 0.05). The protein expression of calpain-2 increased as the dose of BDE-153 rose. Compared with the control group (mRNA: 0.81±0.26; protein: 0.15±0.07), the 5 and 10 mg/kg BDE-153 groups had significantly higher mRNA expression of calpain-2 (5 mg/kg BDE-153 group: 1.16±0.52; 10 mg/kg BDE-153 group: 1.32±0.23) and significantly higher protein expression of calpain-2 (5 mg/kg BDE-153 group: 0.31±0.07; 10 mg/kg BDE-153 group: 0.37±0.06) (P < 0.05). The 10 mg/kg BDE-153 group had significantly higher protein expression of calpain-2 than the 1 mg/kg BDE-153 group (0.37±0.06 vs 0.22±0.07, P < 0.05). CONCLUSION: Ca(2+-) mediated calpain-2 activation may be one of the main mechanisms of BDE-153 neurotoxicity.


Assuntos
Cálcio/metabolismo , Córtex Cerebral/metabolismo , Bifenil Polibromatos/toxicidade , Animais , Animais Recém-Nascidos , ATPase de Ca(2+) e Mg(2+)/metabolismo , Calcineurina/metabolismo , Calpaína/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
9.
Exp Cell Res ; 318(10): 1175-84, 2012 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-22483937

RESUMO

Inflammatory responses are complex events occurring when the host immune system fights against invading pathogens, which are double-edged swords requiring appropriate control. MicroRNAs (miRNAs), emerging as a new layer of gene-regulation mechanism, have been reported to have crucial effects on inflammation. In the current study, we identified miR-34a, previously known for its potent tumor suppressive role, to be a novel inflammation regulator. We found that the expression of miR-34a was downregulated in macrophages after lipopolysaccharide (LPS) stimulation. MiR-34a mimics decreased, while the inhibition of miR-34a increased, the expression of inflammatory cytokines tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) in LPS treated RAW264.7 cells. Bioinformatics predictions revealed a potential binding site of miR-34a in 3' untranslated region (UTR) of Notch1 and it was further confirmed by luciferase assay. Moreover, both the mRNA and protein level of Notch1 were downregulated by miR-34a in RAW264.7. Subsequently, knockdown of Notch1 with either genetic or pharmacological inhibition exhibited similar effects as miR-34a mimics on LPS-induced macrophage inflammatory response. Furthermore, the NF-κB activation induced by LPS was also significantly suppressed by miR-34a. These results together identify, for the first time, miR-34a as a negative regulator in LPS-induced inflammation at least partially by targeting Notch1. Besides extending the knowledge of miR-34a from tumor suppressor to inflammation regulator, this study also provides an implication that compounds which can enhance miR-34a expression or miR-34a itself may hold a promise in anti-inflammatory drugs development.


Assuntos
Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Macrófagos/metabolismo , MicroRNAs/fisiologia , Receptor Notch1/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Sítios de Ligação , Células Cultivadas , Citocinas/biossíntese , Feminino , Regulação da Expressão Gênica , Inflamação/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Conformação de Ácido Nucleico , Interferência de RNA , Receptor Notch1/genética , Transdução de Sinais
10.
Phytomedicine ; 18(8-9): 704-9, 2011 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21277758

RESUMO

Resveratrol (3,4',5-trihydroxy-trans-stilbene), one of secondary metabolites of low molecular weight present in plant, has various important biological effects. It can induce apoptosis in human leukemia cell types in vitro, although the mechanism is not fully understood. In the present study, we demonstrated reduced viability and DNA synthesis, as well as increased proportion of the subdiploid cell population, in HL-60 cells as determined by cell cycle analysis with resveratrol. Resveratrol treatment resulted in a gradual time-dependent decrease in the expression of anti-apoptotic Bcl-2 and increase in that of Bax, annexin A1, growth arrest- and DNA damage-induced gene 45α (GADD45α), and cleaved caspase-3. In addition, resveratrol markedly increased caspase-3 activity in cells. Our results suggest that resveratrol could inhibit the proliferation and induce apoptosis of HL-60 cells through a GADD45α and annexin A1/caspase-3 pathway.


Assuntos
Anexina A1/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Proteínas Nucleares/metabolismo , Estilbenos/farmacologia , Anexina A1/biossíntese , Anexina A1/genética , Apoptose/fisiologia , Caspase 3/metabolismo , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/genética , Processos de Crescimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Fase G1/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas Nucleares/biossíntese , Proteínas Nucleares/genética , Inibidores da Síntese de Ácido Nucleico/farmacologia , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Resveratrol
11.
Zhongguo Fei Ai Za Zhi ; 13(4): 287-91, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20677551

RESUMO

BACKGROUND AND OBJECTIVE: Invasion and metastasis are the primary causes of death in patients with pulmonary carcinoma. The epidermal growth factor (EGF) stimulates A549 cells invasion greatly through activating ERK and PI3K-Akt signaling pathway. The aim of this study is to elucidate the inhibitory effect of Resveratrol on EGF-induced invasive ability of A549 cells in vitro and explore the molecular mechanism. METHODS: The cytotoxicity of Resveratrol was evaluated by methyl thiazolyltetrazolium (MTT) assay. Then, the A549 cells were treated with EGF and non-cytotoxic concentration of Resveratrol. The cells' invasion were detected by Boyden chamber assay; MMP-2 activity was determined by gelatine zymography assay; the changes of the related proteins were detected by Western blot. RESULTS: Resveratrol was not toxic to A549 cells at the concentration between 0 to 30 microM. The invasion ability of EGF-induced A549 cells was decreased after treatment with 20 microM resveratrol for 24 h, accompanied by the inhibition of MMP-2 secretion. And the levels of p-ERK1/2, PI3K (within 6 h) were suppressed too. CONCLUSION: 20 microM Resveratrol inhibits A549 cells' invasion possibly through the suppression of the activation of ERK and PI3K-Akt signaling pathways, subsequently exerting inhibitory effect on MMP-2.


Assuntos
Adenocarcinoma , Anticarcinógenos/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Neoplasias Pulmonares , Estilbenos/farmacologia , Adenocarcinoma/metabolismo , Western Blotting , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Resveratrol , Transdução de Sinais/efeitos dos fármacos
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