Abstract

Objective To investigate the possible mechanism of DDP-resistant phenotype in gastric cancer cell line SGC7901/DDP mediated by Notch1. Methods The Notchl expression was blocked by 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 cy- tometry, and the expression of NF-kappa B (NF-κB) and the muhidrug-resistant protein P-glycoprotein (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 Notchl 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. Key words: Gastric neoplasm ; Multidrug resistance ; P-glycoprotein

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