Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add filters








Year range
1.
Article in Chinese | WPRIM | ID: wpr-906189

ABSTRACT

Objective:To explore the potential targets and related mechanism involved in the paclitaxel resistance to ovarian cancer. Method:Ovarian cancer A2780 cells and A2780 paclitaxel-resistant cells (A2780/T) were treated by 2, 4, 8, 16, 32, 64, 128, 256 μmol·L<sup>-1</sup> paclitaxel (PTX) for 24 h or 48 h respectively <italic>in vitro</italic>. The proliferation rate of A2780 cells and A2780/T cells treated with paclitaxel was determined by methyl thiazolyl tetrazolium (MTT) colorimetric method assay. A2780 and A2780/T cells were analyzed by LC-MS/MS Label-Free quantitative proteomics to identify and screen differentially expressed proteins in the two groups of cells. Gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to determine the potential biomarkers of paclitaxel resistance in ovarian cancer. Conventionally cultured A2780 cells were used as a control group, and A2780/T cells were treated with 0, 1, 4 μmol·L<sup>-1</sup> PTX. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot methods were used to detect and verify the mRNA and protein expression levels of potential target transforming growth factor-<italic>β</italic>-activated kinase 1 binding protein 1 (TAB1) and its downstream related molecules transforming growth factor-<italic>β</italic>-activated kinase (TAK1) and p38. Result:After PTX treatment for 24 h and 48 h, the cell viability of A2780 and A2780/T cells decreased. The inhibitory rate of PTX on A2780 cells was significantly higher than that of A2780/T cells. In A2780 cells, the IC<sub>50</sub> of PTX treatment for 48 h was 0.002 μmol·L<sup>-1</sup>, while in A2780/T cells, the IC<sub>50 </sub>of PTX was greater than the maximum concentration of 128 μmol·L<sup>-1</sup>, indicating that A2780/T cells were resistant to PTX compared with A2780 cells. 441 differentially expressed proteins and 421 special differentially expressed proteins between A2780/T and A2780 cells were screened by label-free quantitative proteomic analysis. GO function enrichment analysis showed that the binding proteins accounted for the majority (80%) among the differentially expressed proteins. According to the results of KEGG pathway analysis and expression site analysis, TAB1 might be a potential biomarker in paclitaxel-resistant ovarian cancer. Compared with A2780 cells, mRNA and protein expression levels of TAB1 in A2780/T cells were significantly reduced (<italic>P</italic><0.01). mRNA expression of TAK1 and p38 that interacted with TAB1 were also significantly reduced (<italic>P</italic><0.05, <italic>P</italic><0.01), while there was no significant change in protein expression. Conclusion:TAB1 may be a potential biomarker of paclitaxel resistance to ovarian cancer , and its mechanism may be related to the TAB1/TAK1/p38 MAPK pathway.

2.
Article in English | WPRIM | ID: wpr-922757

ABSTRACT

During the pathogensis of rheumatoid arthritis (RA), activated RA fibroblast-like synoviocytes (RA-FLSs) combines similar proliferative features as tumor and inflammatory features as osteoarthritis, which eventually leads to joint erosion. Therefore, it is imperative to research and develop new compounds, which can effectively inhibit abnormal activation of RA-FLSs and retard RA progression. Neohesperidin (Neo) is a major active component of flavonoid compounds with anti-inflammation and anti-oxidant properties. In this study, the anti-inflammation, anti-migration, anti-invasion, anti-oxidant and apoptosis-induced effects of Neo on RA-FLSs were explored to investigate the underlying mechanism. The results suggested that Neo decreased the levels of interleukin IL-1β, IL-6, IL-8, TNF-α, MMP-3, MMP-9 and MMP-13 in FLSs. Moreover, Neo blocked the activation of the MAPK signaling pathway. Furthermore, treatment with Neo induced the apoptosis of FLSs, and inhibited the migration of FLSs. It was also found that Neo reduced the accumulation of reactive oxygen species (ROS) induced by TNF-α. Taken together, our results highlighted that Neo may act as a potential and promising therapeutic drug for the management of RA.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Cell Movement , Cell Proliferation , Cells, Cultured , Fibroblasts , Hesperidin/analogs & derivatives , Humans , Synoviocytes , Tumor Necrosis Factor-alpha/genetics
SELECTION OF CITATIONS
SEARCH DETAIL