ABSTRACT
The p21-activated kinase 1 (PAK1) is a member of the P21-activated protein kinase family that plays an important role in the proliferation and on cogenesis of pancreatic cancer. PAK1 is an important target for the treatment of pancreatic cancer. At present, akinase inhibitor targeting PAK1 is still in the preclinical research stage. Therefore, screening for new PAK1 kinase inhibitors is of great significance. In this study the natural compound celastrol was found to have a significant inhibitory effect on PAK1, with an IC50 value of 3.614 μmol·L-1. Molecular docking results showed that celastrol had good binding to PAK1. An MTT assay indicated that celastrol inhibited the proliferation of pancreatic cancer cells BxPC-3 and PANC-1. Mechanistic studies revealed that the inhibition of pancreatic cancer cells by celastrol was reversed by PAK1 siRNA. Celastrol inhibited PAK1 and the subsequent activation of downstream signaling pathways, thereby activating apoptosis signaling pathways and triggering apoptosis in pancreatic cancer cells. These findings suggested that celastrol induced apoptosis in pancreatic cancer cells by suppressing the PAK1 kinase signaling pathway and has potential value for the treatment of pancreatic cancer.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the disinfection of wastewater in China.</p><p><b>METHODS</b>During the SARS epidemic occurred in Beijing, a study of different disinfection methods used in the main local wastewater plants including means of chlorine, chlorine dioxide, ozone, and ultraviolet was carried out in our laboratory. The residual coliform, bacteria and trihalomethanes, haloacetic acids were determined after disinfection.</p><p><b>RESULTS</b>Chlorine had fairly better efficiency on microorganism inactivation than chlorine dioxide with the same dosage. Formation of THMs and HAAs does not exceed the drinking water standard. UV irradiation had good efficiency on microorganism inactivation and good future of application in China. Organic material and ammonia nitrogen was found to be significant on inactivation and DBPs formation.</p><p><b>CONCLUSION</b>Chlorine disinfection seems to be the best available technology for coliform and bacteria inactivation. And it is of fairly low toxicological hazard due to the transformation of monochloramine.</p>