Inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism

Pancreatic ductal adenocarcinoma(PDAC) is one of the five most malignant cancer.ZX-1201 is one of the active constituents in Alismatis Rhizoma,a well-known traditional Chinese medi.cine with a wide variety of pharmacological properties including diuretic,anti-hyperlipidemic,anti-atheroscle.rotic,anti-cancer,anti-inflammatory and anti-oxidative activities.We investigated the inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism in vitro and in vivo.ZX-1201 inhibited the growth and metastasis of PANC-1 cells in BALB/c nude mice significantly.ZX-1201 inhibited the function of AQP1 via directly interaction and involved in the reversion process of ZX-1201 on TGF-β_1.CTGF was an important protein in the reversion process of ZX-1201 on TGF-β_1.ZX-1201 inhibited the migration of PANC-1 and CPFAC-1 cells induced by TGF-β_1 in vitro.ZX-1201 reversed the down-regu.lated of epithelial markers and up-regulated of mesenchymal markers,as well as the up-regulated of Snail and p-Smad2/3 induced by TGF-β_1.And ZX-1201 reversed Epithelial-Mesenchymal Transition by down-regulating AQP1 and inhibiting translocation of β-catenin,the promotor of CTGF.According to these,ZX-1201 inhibited the migration of pancreatic cancer cells.We concluded that ZX-1201 inhibited the growth and metastasis of PANC-1 cells in vivo significantly.And AQP1,β-catenin and CTGF were the pivotal proteins in the process of ZX-1201 inhibiting PANC-1 cells migration induced by TGF-β_1.