RESUMO
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant carcinomas, which is characterized by apoptosis- and autophagy-dependent tumorigenic growth. Autophagy constitutes a stress adaptation that suppresses apoptosis. To explore new leading compound against PDAC, a pectin-like polysaccharide named RP02-1, was purified from roots of Polygala tenuifolia. Bioactivity test showed that RP02-1 might inhibit pancreatic cancer cells growth in vitro and in vivo. RP02-1 could inhibit pancreatic cancer cell (AsPC-1 and BxPC-3) proliferation, migration and colony formation. Mechanism study suggested that RP02-1 induced pancreatic cancer cells apoptosis, which was detected by Bcl-2 down-regulation, Bax up-regulation and conversion from Caspase 3 to Cleaved Caspase 3. Interestingly, autophagy was suppressed by RP02-1 treatment concentration-dependently through affenuatingBeclin-1, ATG5 and LC3B expression in BxPC-3 cells. In addition, RP02-1 could inhibit autophagy induced by Pennogenin 3-O-beta-chacotrioside. However, RP02-1 had almost no toxicity both in vitro and in vivo. The above results suggested that RP02-1 might be a potential leading compound for new drug candidate development for human PDAC treatment via inducing apoptosis and against autophagy.