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1.
Braz. j. med. biol. res ; 44(2): 91-99, Feb. 2011. ilus, tab
Article Dans Anglais | LILACS | ID: lil-573653

Résumé

Searching for effective Smad3 gene-based gene therapies for hepatic fibrosis, we constructed siRNA expression plasmids targeting the rat Smad3 gene and then delivered these plasmids into hepatic stellate cells (HSCs). The effect of siRNAs on the mRNA levels of Smad2, Smad3, Smad4, and collagens I-α1, III-α1 and IV-α1 (Colα1, Col3α1, Col4α1, respectively) was determined by RT-PCR. Eighty adult male Sprague-Dawley rats were randomly divided into three groups. Twice a week for 8 weeks, the untreated hepatic fibrosis model (N = 30) and the treated group (N = 20) were injected subcutaneously with 40 percent (v/v) carbon tetrachloride (CCl4)-olive oil (3 mL/kg), and the normal control group (N = 30) was injected with olive oil (3 mL/kg). In the 4th week, the treated rats were injected subcutaneously with liposome-encapsulated plasmids (150 µg/kg) into the right liver lobe under general anesthesia once every 2 weeks, and the untreated rats were injected with the same volume of buffer. At the end of the 6th and 8th weeks, liver tissue and sera were collected. Pathological changes were assessed by a semi-quantitative scoring system (SSS), and a radioimmunoassay was used to establish a serum liver fibrosis index (type III procollagen, type IV collagen, laminin, and hyaluronic acid). The mRNA expression levels of the above cited genes were reduced in the HSCs transfected with the siRNA expression plasmids. Moreover, in the treated group, fibrosis evaluated by the SSS was significantly reduced (P < 0.05) and the serum indices were greatly improved (P < 0.01). These results suggest that Smad3 siRNA expression plasmids have an anti-fibrotic effect.


Sujets)
Animaux , Mâle , Rats , Régulation négative/génétique , Cellules étoilées du foie/métabolisme , Cirrhose expérimentale/métabolisme , ARN messager/génétique , Petit ARN interférent/usage thérapeutique , /métabolisme , Tétrachloro-méthane , Collagène/métabolisme , Liposomes , Cirrhose expérimentale/induit chimiquement , Cirrhose expérimentale/génétique , Cirrhose expérimentale/anatomopathologie , Plasmides , Dosage radioimmunologique , Répartition aléatoire , Rat Sprague-Dawley , RT-PCR , Interférence par ARN , ARN messager/métabolisme , Indice de gravité de la maladie , /génétique , Transfection , Facteur de croissance transformant bêta-1/génétique , Facteur de croissance transformant bêta-1/métabolisme
2.
Braz. j. med. biol. res ; 39(5): 677-685, May 2006. ilus, graf
Article Dans Anglais | LILACS | ID: lil-425788

Résumé

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 æM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 ± 3.9 percent in HNE1-LMP1 cells vs 37.89 ± 4.9 percent in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9 percent), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1 percent), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27 percent) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.


Sujets)
Humains , Antinéoplasiques/pharmacologie , Composés de l'arsenic/pharmacologie , Matrix metalloproteinase 9/effets des médicaments et des substances chimiques , Tumeurs du rhinopharynx/traitement médicamenteux , Oxydes/pharmacologie , Protéines de la matrice virale/effets des médicaments et des substances chimiques , Technique de Western , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Survie cellulaire/effets des médicaments et des substances chimiques , Technique d'immunofluorescence , Régulation de l'expression des gènes tumoraux , Microscopie confocale , Matrix metalloproteinase 9/génétique , Tumeurs du rhinopharynx/anatomopathologie , Invasion tumorale/anatomopathologie , Métastase tumorale/anatomopathologie , RT-PCR , ARN messager/effets des médicaments et des substances chimiques , Protéines de la matrice virale/génétique
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