Original Article Overexpression of CDX2 in gastric cancer cells promotes the development of multidrug resistance

摘要: Modulator of multidrug resistance (MDR) gene is a direct transcriptional target CDX2. However, we still speculate whether CDX2 affects MDR through other ways. In this study, cisplatin-resistant (SGC7901/DDP) and 5-fluoro-2, 4(1h,3h)pyrimidinedione-resistant (BGC823/5-FU) gastric cancer cell line with stable overexpression were established. The influence on was assessed by measuring IC50 SGC7901/DDP BGC823/5-FU cells to cisplatin, doxorubicin, 5-fluorouracil, rate doxorubicin efflux, apoptosis, cycle progression detected flow cytometry. addition, determined the in vivo effects CDX2-overexpression lentiviral vector (LV-CDX2-GFP) tumor size, apoptotic tissues deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling hematoxylin eosin stain- ing. Results showed that LV-CDX2-GFP led up-regulation mRNA protein expression. It significantly inhibited sensitivity 5-fluorouracil. Flow cytometry confirmed percentage decreased after up-regulation. This notion further supported observation blocked entry into M-phase cycle. Furthermore, intracellular accumulation doxorubicin. molecular studies, quantitative reverse-transcriptase real-time polymerase chain reaction western blotting revealed could suppress expression Caspase-3, Caspase-9 PTEN, increased MDR1, MRP, mTOR, HIF-1α.