Objective: To observe the inhibitory effect of Compound phyllanthus Urinsria Ⅱ(CPUⅡ) on formation of liver cancer in rats induced by diethylnitrosamine (DEN)

and explore its anti-cancer mechanism. Method: Two hundred and forty SPF grade Wistar male rats were randomly divided into normal group

model group

CPU II high dose group (23.14 g·kg-1)

low dose group (11.57 g·kg-1)

and tegafur group. Rat models of liver cancer were induced by DEN for eighteen weeks

and medicine intervention was done at the same time according to the experimental design for eighteen weeks. 8 rats were sacrificed in each group after treatment for every 6 weeks

to observe the general condition

hepatic function index and nodule formation of liver cancer of the rats. Pathologic changes of liver tissues were observed under microscope. Radioimmunoassay method was used to determine the levels of interleukin(IL)-6 in serum of rats. Gene expression levels of mRNA and protein related to IL-6 signal pathway and microRNA let-7a regulatory network of the liver tissues were detected respectively by real-time fluorescent quantitative PCR and Western blot method. Result: At the end of eighteenth week

the number of nodules of liver cancer in rats of CPU II high dose group and low-dose group was significantly reduced as compared with that in the model group (P<0.05);levels of IL-6

ALT and AST in serum of rats in CPU II high dose group and low dose group were significantly decreased (P<0.05);the expression level of microRNA let-7a in liver tissues increased obviously in CPU II high dose group as compared with that in model group

while the mRNA expression levels of NF-κB-p65

IL-6

STAT3

RAS and c-myc genes were significantly decreased (P<0.05). The protein expression levels of STAT3 and p-STAT3 were also obviously reduced in CPU II high dose group and low dose group as compared with that in model group (P<0.05). Conclusion: CPUⅡcan effectively inhibit the formation of liver cancer in rats induced by DEN through inhibiting IL-6 expression and activation of IL-6/STAT3 signaling pathway

and its mechanism may be related with up-regulating microRNA let-7a expression and down-regulating NF-κB-p65 expression.