Berberine exerts pro-apoptotic effects on PC-9 cells via activation of JNK/FOXO3 signaling / 中国肿瘤临床

ABSTRACT

Objective:To investigate the pro-apoptotic effect of berberine (Ber) on human lung adenocarcinoma PC-9 cell line, and to detect the role of c-Jun N-terminal kinase (JNK)/forkhead box protein O3 (FOXO3) signaling in this process. Methods:The PC-9 cells were randomly divided into the control group and the Ber group, which was treated with 30 and 60μM Ber. The survival rate, apoptot-ic rate, ROS generation, caspase-3 activity, and mitochondrial membrane potential of cells were detected. Western blot was per-formed to detect the expression of JNK/FOXO3 signaling and apoptosis-related proteins. A JNK-specific activation inhibitor, SP600125, was used to block the phosphorylation of FOXO3 in PC-9 cells, and then treated with Ber (30 and 60μM) for further detection after 24 h. Results:Ber treatment resulted in an obvious reduction in cell viability, promotion of cell apoptosis, downregulation of mitochondri-al membrane potential, and an increase of ROS and caspase-3 in a dose-dependent manner. Western blot analysis demonstrated that Ber treatment resulted in a significant upregulation of p-JNK, FOXO3, and Bax expression, and a downregulation of p-FOXO3 and Bcl2 levels. Moreover, the inhibition of JNK activation by SP600125 antagonized the anti-FOXO3 phosphorylation role and the pro-apoptotic role of Ber on PC-9 cells. Conclusion:Ber treatment effectively inhibits the viability of PC-9 cells and enhances apoptosis and oxidative stress injury, which may be related to the upregulation of p-JNK and FOXO3 and the downregulation of p-FOXO3.