ABSTRACT
<p><b>OBJECTIVE</b>To investigate whether transcription factor-kappaB (NF-κ B) is involved in the modulation of P-glycoprotein (P-gp) by glucosylceramide synthase (GCS) in a multidrug resistance leukemia cell line K562/A02 and to explore the relationship between NF-κ B and extracelluar signal-regulated kinase (ERK).</p><p><b>METHODS</b>K562/A02 cells were treated with GCSsiRNA, pyrrolidine dithiocarbamate (PDTC, a NF-κ B specific inhibitor) and U0126 (a MEK1/2 inhibitor), respectively. The expression of GCS and multidrug resistance protein 1 (MDR1) mRNA were analyzed with qRT-PCR. Various proteins of different groups were measured by Western blotting.</p><p><b>RESULTS</b>After transfected with GCSsiRNA for 48 h, GCS mRNA were reduced by 62% (51%-73%) and MDR1 mRNA was reduced by 52% (43%-61%) in the K562/A02 cells. Compared with the negative control, relative expression of NF-κ B p65 in nuclear and P-ERK1/2 were both down-regulated, and P-gp was also inhibited significantly at 72 h after transfected with GCSsiRNA (P< 0.05). In addition, the expression of P-gp was decreased at 24 h with 80 μ mol/L PDTC and 48 h with 20 μ mol/L PDTC. P-ERK1/2 was inhibited significantly when the cells were treated with 20 μ mol/L U0126 for 48 h. The expression of NF-κ B p65 in nuclear and P-gp were also down-regulated.</p><p><b>CONCLUSION</b>NF-κ B can modulate the effect of GCS on P-gp in K562/A02 cells. P-ERK1/2 can activate NF-κ B in above signal transduction pathway.</p>
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Metabolism , Cell Line, Tumor , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Glucosyltransferases , Genetics , Metabolism , K562 Cells , Leukemia , Genetics , NF-kappa B , Genetics , MetabolismABSTRACT
AIM: To explore the effects of Angelicae sinensis preparation and sodium ferulate on inflammatory liver injury induced by lipopolysaccharide (LPS) and their molecule mechanism. METHODS: ICR mice were divided into five groups: Angelicae sinensis group, sodium ferulate group, dexamethasone group, inflammation control group and normal group. The model of inflammatory injury in mice was set up by tail vein injection with the bacillus calmette-guerin (BCG) and LPS respectively prior and posterior to administration of those tested drugs. The tested drugs (the preparations of Angelica sinensis, sodium ferulate and dexamethasone) and normal saline were given respectively to the corresponding group. The pathological observation of the liver tissues in mice was made for the intensity of inflammatory liver injuries. The immunohistochemical detection and comparison were performed for the expression of ICAM-1 and E-selectin proteins in the liver tissues in those mice. RESULTS: The intensities of liver inflammatory injuries in mice from drug-treated groups were obviously lighter than that from the inflammation control group (P
ABSTRACT
AIM: To find out whether traditional Chinese medicine Angelicae Sinensis has direct suppressive effect on schistosome egg-induced granulomatous response. METHODS: The lung model of granuloma response was established by injecting living eggs of Schistosoma japonicum into the tail veins of eggs-sensitized mice then the preparation of Angelicae Sinensis were given intraperitoneally once a day for ten days. In vitro model of granulomatous reaction was set up by incubating dry schistosome eggs together with those splenocytes isolated from schistosome infected-mice or from the mice with pulmonary granuloma formation. Different doses of the preparation was, in the need of experiment, added to culture fluid. The sizes of granulomas formed surrounding single egg in lungs or the intensity of in vitro granulomatous responses were measured and observed. RESULTS: The average diameter of pulmonary granulomas in administered group was significantly smaller than that of the control ( P
ABSTRACT
AIM:To explore whether cyclosporine A (CsA) can regulate the expression of nometastatic gene23 H1 type (nm23-H1) in human choriocarcinoma Bewo cells,in order to seek new proof of treating trophoblast diseases.METHODS:The Bewo cells were divided into two groups. The vehicle control group,and the CsA group with different concentrations from 10-2 ?mol/L to 10 ?mol/L. The effect of CsA on the transcription of nm23-H1 was determined by reverse transcription-polymerase chain reaction (RT-PCR) after cultured for 48 h and protein level of nm23-H1 was determined by In-cell Western after cultured for 72 h.RESULTS:Compared to the vehicle group,CsA significantly downregulated the transcription and translation of nm23-H1 in a dose-dependent manner from 10-2 ?mol/L to 10 ?mol/L,and the inhibition reached its top when concentration of CsA was 1.0 ?mol/L (P