The Effect Of Darbufelone On Growth Of SGC-7901 Cell Line And Its Possible Mechanism

Objective: To evaluate the efficacy of dual COX–2/5–LOX inhibitor darbufelone on the proliferation and apoptosis of human gastric carcinoma cell line SGC–7901, and to explore the mechanisms of apoptosis induced by darbufelone. To detect the expression of COX–2 and 5–LOX in gastric cancer tissue.Methods: MTT assay was used to detect the inhibition of gastric adenocarcinoma cell line SGC–7901 treated with darbufelone in different concentrations and at different times. TUNEL staining was used to evaluate the apoptosis of SGC–7901 cells. The changes of COX–2, 5–LOX, Bax, Bcl–2 and caspase–3 mRNA expression were studied by reverse transcription polymerase chain reaction. COX–2, 5–LOX, Bax, Bcl–2 and caspase–3 protein expression were analyzed by immunocytochemistry. Flow cytometer was used to determine the mitochondrial membrane potential and ROS. The expression of 5–LOX protein and COX–2 protein in gastric cancer tissues were detected by immunohistochemistry.Results: Darbufelone significantly inhibited SGC–7901 cell line proliferation, as well as increased the apoptosis ratio of SGC–7901 in dose–dependent manner. Compared with control group, the expression of Bcl–2, COX–2, 5-LOX and mitochondrial membrane potential were dropped, Bax, caspase–3 and ROS were elevated. The AOD of COX–2 and 5–LOX protein expression were 0.39±0.12 and 0.42±0.14 in gastric cancer, higher than those in the corresponding normal gastric mucosa tissues (P<0.05).Conclusion: Darbufelone can inhibit the proliferation and induce apoptosis of SGC–7901 cells by increasing intracellular ROS and decreasing mitochondrial membrane potential. Expressions of 5–LOX and COX–2 in gastric cancer tissue were much higher than those in the corresponding normal gastric mucosa tissues, and this indicate that darbufelone may have potential effect in the treatment of gastic cancer.