Non-small cell lung carcinoma (NSCLC) is the most common lung cancer with high morbidity and mortality. The traditional treatment for NSCLC is particularly liable to relapse with many side-effects. Barbaloin is a natural compound with anticancer efficacy. The present study aimed to investigate the anticancer potential of barbaloin in NSCLC. The results displayed that barbaloin inhibited the viability of A549 cells by decreasing cell growth and the expression level of Ki-67 and proliferating cell nuclear antigen (PCNA), especially at high concentrations (50 and 100 µM). Besides, barbaloin increased the apoptosis rate of A549 cells and induced an accumulation of G2/M phase. Increased expression of apoptosis-related proteins (caspase-3, -8 and -9) and the changed levels of cell cycle checkpoint proteins (p27, p53 and cyclin A) further convinced of the anti-viability effect of barbaloin in A549 cells. On the other hand, barbaloin significantly suppressed the invasion and migration of A549 cells, and restrained the expression of tumor metastasis-related proteins. We further explored the activation of pro-survival or pro-metastasis signaling pathways, including AKT, nuclear factor kappa B (NF-κB), mitogen-actived protein kinase (MAPK) and β-catenin. The results revealed that barbaloin inactivated the p38MAPK/Cdc25B/Hsp27 pathway by inhibiting p38 nucleus translocation, while no significant influence was observed among other pathways. Finally, barbaloin restrained the growth and hepatic metastases of A549 cells in vivo. Taken together, our research indicated that barbaloin inhibited the proliferation and metastasis of NSCLC cells in vivo and in vitro. This may provide safer and more effective aspects for the treatment of NSCLC.
During cardiac pulmonary bypass (CPB), myocardial ischemia-reperfusion (I/R) induces heart glucose metabolism impairment. Our previous research showed that the decreased glucose utilization is due to decreased glucose transporter-4 (Glut-4) expression and translocation to myocyte surface membranes. This study further examined whether rosiglitazone, a synthetic agonist of peroxisome proliferator-activated receptor γ, could intervene glucose metabolism by regulating Glut-4 mRNA during I/R in dogs. Cardiac ischemia was induced by cardiopulmonary bypass for 30 or 120 min. Plasma insulin and glucose concentrations were measured at pre-bypass (control), aortic cross-clamp off (I/R) at 15, 45, and 75 min. The left ventricle biopsies were taken for the expression of Glut-4 mRNA by real-time RT-PCR. In dogs receiving 120 min ischemia, coronary arterial, venous glucose concentrations, plasma insulin levels, and insulin resistant index (IRI) were increased, but the expression of Glut-4 mRNA was decreased obviously at 15 min of reperfusion, and recovered gradually. On the other hand, these changes were relatively mild in dogs treated with rosiglitazone in cardioplegic solution and expression of Glut-4 mRNA was increased remarkably. It is concluded that the decrease in total amount of Glut-4 mRNA expression could be one of the important molecular mechanisms, which causes the myocardium insulin resistance. The longer the ischemia period, the decrease in amount of Glut-4 mRNA was more dramatic. Adding rosiglitazone into the cardioplegic solution during I/R can increase the amount of Glut-4 mRNA expression, mitigate the myocardium insulin resistance and improve the myocardium I/R injury during CPB.
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