ABSTRACT
Aim To observe the effect of Salvianolic-aid B ( Sal B ) on the progression of hepatic fibrosis-carcinoma in mice induced by diethylnitrosamine ( DEN ) and investigate the mechanism of Sal B in-volved in the shift between pSmad 3 C/p21-mediated tumor suppressive signaling and pSmad 3L/PAI-1/c-Myc-mediated pro-fibrogenic/oncogenic signaling . Methods A total of 100 male Kunming mice were randomly grouped , DEN-induced hepatic fibrosis-car-cinoma model of mice was established , which was in-tragastrically treated by Sal B with two dosages ( 15 , 30 mg · kg -1 ) and colchicine with one dosage ( 0.2 mg· kg -1 ) , respectively.The mice were sacrificed at 12th week or 16th week after the start of DEN adminis-tration.Pathological changes of livers in each group were assessed by liver biopsy , hematoxylin-eosin ( HE ) staining and Van Gieson ( VG ) staining .The protein expressions of pSmad3C, pSmad3L, p21, plas-minogen activator inhibitor-1 ( PAI-1 ) and c-Myc in liver tissues were assayed by Western blot .Results In the normal control group , the surface of mouse liver was smooth and soft , and the structure of the hepatic lobule was intact.In the DEN alone group, at 12th week, the surface of mouse liver was rough and hard , the hepatic lobule was encysted or separated by colla-gen bundles, and pseudolobules emerged.At 16th week, the surface of mouse liver in the DEN alone group was rough with some nodules. HE and VG staining showed that the hepatocytes of nodules with obvious atypia and hyperchromatic nuclei were veri-fied.However, these pathological changes were evi-dently improved in Sal B treatment groups compared with the DEN group , which was proved by reductive cirrhotic nodules and alleviative fibrosis at 12th week, and decreasing cancerous nodes and ameliorative dif-ferentiation via Sal B treatment at 16th week.Western blot results showed that the protein expression of pS-mad3C, pSmad3L, PAI-1 were less, and c-Myc ex-pression was scarcely found in normal group; in DEN alone group, at 12th week, the protein expression of pSmad3C had no significant change , while the protein levels of pSmad3L, PAI-1, p21 were up-regulated, and at 16th week, the protein expressions of pS-mad3C, pSmad3L, p21, PAI-1 and c-Myc increased. In Sal B treatment group, the expressions of p21 and pSmad3C increased significantly , pSmad3L and PAI-1 protein levels markedly decreased at 12th week, the expression of pSmad3C increased obviously , p21 was almost unchanged , and the expression of pSmad 3L, PAI-1 and c-Myc were significantly reduced at 16th week .Conclusions Sal B could delay the progression of hepatic fibrosis-carcinoma in mice induced by DEN , and the mechanism may involve mediating the shift of pSmad3C/p21 and pSmad3L/PAI-1/c-Myc signaling.