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- 저자 : Mei Nu Cui (검색결과 2 건)
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Depletion of BIS sensitizes A549 cells to treatment with cisplatin
Mei Nu Cui,윤혜현,이난이,김혜윤,임창임,김용삼,이정화 대한독성 유전단백체 학회 2016 Molecular & cellular toxicology Vol.12 No.1
Bcl-2 interacting cell death suppressor (BIS), an anti-stress and ant-apoptotic protein, has been reported to be expressed at high levels in various cancers. In a previous study, we reported on a high level of expression of BIS in non small cell lung cancer tissues. To explore the significance this finding in lung cancer, in this study, we investigated the effect of BIS depletion on the survival of A549 cells upon treatment with anti-tumor agents. BIS knock out A549 cells, prepared by the CRISPR/Cas9 system, revealed a substantial decrease in survival to cisplatin treatment. Western blotting and quantitative real time PCR assays indicated that, among the anti-apoptotic Bcl-2 family proteins, the expression of Mcl-1 was decreased by BIS depletion at the protein level not at the mRNA level. Since BIS expression has been shown to be regulated by HSF1, we subsequently illustrated the sensitization effect of KRIBB11, a HSF1 inhibitor, on cisplatin-induced toxicity in A549 cells, accompanied by a decrease in both BIS and Mcl-1 expression. Our results suggest that BIS-mediated Mcl-1 stabilization represents a potential therapeutic target for cancer therapy.
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( Young Dae Lee ),( Mei Nu Cui ),( Hye Hyeon Yoon ),( Hye Yun Kim ),( Il Hoan Oh ),( Jeong Hwa Lee ) 생화학분자생물학회 2014 BMB Reports Vol.47 No.5
Bcl-2 interacting cell death suppressor (Bis) has been shown tohave anti-apoptotic and anti-stress functions. Recently, increasedBis expression was reported to correlate with gliomaaggressiveness. Here, we investigated the effect of Bis knockdownon the acquisition of the invasive phenotype of A172glioma cells, induced by 12-O-Tetradecanoylphorbol- 3-acetate(TPA), using a Transwell assay. Bis knockdown resulted in asignificant decrease in the migration and invasion of A172cells. Furthermore, Bis knockdown notably decreased TPAinducedmatrix metalloproteinase-9 (MMP-9) activity andmRNA expression, as measured by zymography and quantitativereal time PCR, respectively. A luciferase reporter assayindicated that Bis suppression significantly down-regulatedNF-κB-driven transcription. Finally, we demonstrated that therapid phosphorylation and subsequent degradation of IκB-αinduced by TPA was remarkably delayed by Bis knockdown. These results suggest that Bis regulates the invasive ability ofglioma cells elicited by TPA, by modulating NF-κB activation,and subsequent induction of MMP-9 mRNA.[BMB Reports 2014; 47(5): 262-267]
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