Cyclooxygenase-2 inhibitor NS398 enhances radiosensitivity of radioresistant esophageal cancer cells by inhibiting AKT activation and inducing apoptosis.
This study aimed to evaluate the radiosensitizing effect of a COX-2 inhibitor, NS398, and its mechanism in radioresistant esophageal cancer Eca109R50Gy cells. NS398 enhanced radiosensitivity of Eca109R50Gy cells, characterized by redistribution of cell cycle, inhibition of DNA-dependent protein kinase catalytic subunit expression and induction of apoptosis. NS398 also reduced phospho-AKT level, upregulated expression of Bax and both procaspase-3 and active caspase-3, and downregulated Bcl-2 expression. Finally, NS398-induced radiosensitization was partly reversed by insulin-like growth factor-1, but not by prostaglandin E2. Our results suggest that NS398 may enhance radiosensitivity of Eca109R50Gy cells through blocking AKT activation and inducing apoptosis.
Che
Shao-Min
SM
Department of Human Anatomy, Histology and Embryology, Xi'an Jiaotong University School of Medicine, China.
Zhang
Xiao-Zhi
XZ
Hou
Lei
L
Song
Tian-Bao
TB
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation; D004938:Esophageal Neoplasms; D006801:Humans; D009578:Nitrobenzenes / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D011838:Radiation-Sensitizing Agents; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051057:Proto-Oncogene Proteins c-akt