CAJ | 학술논문

目的探讨Notchl参与胃癌SGC7901/DDP细胞株顺铂耐药的机制.方法应用Notchl通路抑制剂MW167抑制Notchl在敏感株SGC7901和耐药株SGC7901/DDP中的表达,通过噻唑蓝(MTT)比色法检测药物敏感性,流式细胞术分析细胞凋亡率,逆转录-聚合酶链反应(RTPCR)和Western blot检测敏感株SGC7901和耐药株SGC7901/DDP中Notch1和NF-kappa B(NF-κB),耐药蛋白P-糖蛋白(P-gP)的表达变化.结果 MW167抑制Notch1表达后敏感株SGC7901和耐药株SGC7901/DDP的药物敏感性显著增加,细胞凋亡率分别为23.71%和12.48%(P＜0.01),NF-κB和耐药蛋白P-gP在基因和蛋白表达水平均明显减低(P＜0.01).结论 Notch1可通过调节P-gP表达及抗凋亡信号通路参与胃癌顺铂耐药,可成为逆转胃癌耐药的新的靶点.
목적 탐토Notchl삼여위암SGC7901/DDP세포주순박내약적궤제.방법 응용Notchl통로억제제MW167억제Notchl재민감주SGC7901화내약주SGC7901/DDP중적표체,통과새서람(MTT)비색법검측약물민감성,류식세포술분석세포조망솔,역전록-취합매련반응(RTPCR)화Western blot검측민감주SGC7901화내약주SGC7901/DDP중Notch1화NF-kappa B(NF-κB),내약단백P-당단백(P-gP)적표체변화.결과 MW167억제Notch1표체후민감주SGC7901화내약주SGC7901/DDP적약물민감성현저증가,세포조망솔분별위23.71%화12.48%(P＜0.01),NF-κB화내약단백P-gP재기인화단백표체수평균명현감저(P＜0.01).결론 Notch1가통과조절P-gP표체급항조망신호통로삼여위암순박내약,가성위역전위암내약적신적파점.
Objective To investigate the possible mechanism of DDP-resistant phenotype in gastrie cancer cell line SGC7901/DDP mediated by Notchl.Methods The Notchl expression was blocked bv the Notchl inhibitor MW167 in both the drug-sensitive cell line SGC7901 and the DDP-resistant cell line SGC7901/DDP.Then this study detected the drug sensitivity by MTT assay,apoptosis rate by flow cytometry,and the expression of NF-kappa B(NF-κB)and the muhidrug-resistant protein P-glyeoprotein (P-gp)by RT-PCR and Western blot in both the mRNA and protein levels.Results The inhibition of Notchl by MW167 resulted in increased drug sensitivity of both SGC7901 and SGC7901/DDP cell lines,with apoptosis rate being 23.71%and 12.48%respectively,and also the down-regulation of NF-κB and P-gP in both mRNA and protein levels(P＜0.01).Conclusion The Notch1 mediated the DDP-resistant phenotype through P-gP expression and anti-apoptosis signal pathway in gastric cancer,which would be a novel and promising target gene for reversing MDR.