Berberine, a natural plant alkaloid, synergistically sensitizes human liver cancer cells to sorafenib.

Sorafenib resistance is one of the major factors affecting the prognosis of patients with hepatocellular carcinoma (HCC). Increasing evidence has indicated that certain traditional medicines can enhance the sensitivity of cancer cells to sorafenib. Berberine, an isoquinoline alkaloid, has been demonstrated to possess antitumor properties against various malignancies. However, the synergistic effect of the combination of berberine and sorafenib in HCC remains unknown. The aim of the present study was to determine the effects of berberine and sorafenib combination on the growth of liver cancer cells. Initially, it was observed that the combination of sorafenib and berberine exerted a synergistic inhibitory effect on the proliferation of SMMC­7721 and HepG2 cells in a dose­ and time­dependent manner by an MTS assay. Edu staining and colony formation assays also revealed that the combination of 100 µM berberine and 4 µM sorafenib exhibited a significant anti­proliferation effect on SMMC­7721 and HepG2 cells. Furthermore, western blotting assay indicated that the expressions levels of cleaved poly(ADP­ribose) polymerase and cleaved caspase­3 increased, while those of the anti­apoptotic protein B­cell lymphoma 2 and vascular endothelial growth factor decreased. To the best of our knowledge, this is the first study to demonstrate that berberine sensitized liver cancer cells to sorafenib treatment. These results suggest that berberine combined with sorafenib is able to inhibit the proliferation of liver cancer cells and induce apoptosis, which provides evidence for further clinical investigation in HCC patients with sorafenib resistance.

[Establishment of a rat model of acute liver failure by a modified 90% bloodless hepatectomy and by D-galactosamine and lipopolysaccharide injection].

OBJECTIVE: To compare the effects of different approaches to establishing rat models of acute liver failure (ALF). METHODS: Sixty-eight Sprague-Dawley rats were randomly divided into 3 groups for establishing ALF models using 3 different approaches, namely conventional hepatectomy for resecting 90% liver tissue as described by Higgins and Anderson, modified bloodless hepatectomy for resecting 90% liver tissue, and intraperitoneal injections of 700 mg/kg D-galactosamine (D-gal) and 5 µg/kg lipopolysaccharide (LPS). The mortality of the rats due to postoperative bleeding and survival rate at 7 days after the surgery were recorded. The levels of alanine aminotransferase (ALT), total bilimbin (Tbil), albumin (ALB), NH3, glucose (Glu) and prothrombin time (PT) were monitored, and histopathologies of the liver were examined at 24 and 72 h after the surgery. RESULTS: The mortality rate due to postoperative bleeding was higher in conventional hepatectomy group than in the modified surgical group (15% vs 0). The survival rate at 7 days was 25%, 0%, 15% in conventional surgical group, modified surgical group and drug injection group, respectively. In the latter two groups, significant changes of ALT, Tbil, ALB, NH3, Glu, and PT were recorded at 24 and 72 h after the modeling (P<0.05), and these changes were the most obvious at 24 h in modified surgical group and at 72 h in the drug injection group; ALB in both groups declined to the lowest at 7 days and then increased gradually. Liver cell degeneration and necrosis were found in modified surgical group and drug injection group at 24 h and 72 h after the modeling. CONCLUSION: Both the modified 90% bloodless hepatectomy and injections of D-gal and LPS can be used to establish ideal rat models of ALF to suit different ALF-related researches.