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Background: Hepatocyte carcinoma (HCC) is one of the most common malignancies worldwide. Despite many achievements in diagnosis and treatment, HCC mortality remains high due to the malignant nature of the disease. Novel approaches, especially for targeted therapy, are being extensively explored. Gene therapy is ideal for such purpose for its specific expression of exogenous genes in HCC cells driven by tissue-specific promoter. However strategies based on correction of mutations or altered expressions of genes responsible for the development/progression of HCC have limitations because these aberrant molecules are not presented in all cancerous cells. In the current work, we adopted a novel strategy by targeting the DNA replication step which is essential for proliferation of every cancer cell. Methods: A recombinant adenovirus with alpha fetoprotein (AFP) promoter-controlled expressions of artificial microRNAs targeting DNA polymerases α, δ, ε and recombinant active Caspase 3, namely Ad/AFP-Casp-AFP-amiR, was constructed. Results: The artificial microRNAs could efficiently inhibit the expression of the target polymerases in AFP-positive HCC cells at both RNA and protein levels, and HCC cells treated with the recombinant virus Ad/AFP-Casp-AFP-amiR exhibited significant G0/1 phase arrest. The proliferation of HCC cells were significantly inhibited by Ad/AFP-Casp-AFP-amiR with increased apoptosis. On the contrary, the recombinant adenovirus Ad/AFP-Casp-AFP-amiR did not inhibit the expression of DNA polymerases α, δ or ε in AFP-negative human normal liver cell HL7702, and showed no effect on the cell cycle progression, proliferation or apoptosis. Conclusions: Inhibition of DNA polymerases α, δ and ε by AFP promoter-driven artificial microRNAs may lead to effective growth arrest of AFP-positive HCC cells, which may represent a novel strategy for gene therapy by targeting the genes that are essential for the growth/proliferation of cancer cells, avoiding the limitations set by any of the individually altered gene. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of Yugan Sanjie decoction on the expressions of regulatory T cells (Tregs), serum P21 protein and vascular endothelial growth factor (VEGF) in mice with hepatocellular carcinoma. Methods: A total of forty specific-pathogen-free (SPF) Kunming mice were randomly assigned to four groups of 10 mice each. Except for normal control group, the other three groups were transfected with hepatoma-22 (H22) cells to establish a mouse model of liver cancer. Mice in the cyclophosphamide group was given cyclophosphamide at a dose of 20 mg/kg daily intragastrically, while those in decoction group were treated with Yugan Sanjie decoction (0.4 ml/kg/day) intraperitoneally. After 30 days of treatment, serum levels of CD4+Th17, CD4+CD25+ Treg, Th17/Treg, TNF-α, and VEGF were determined. Results: There was lower serum level of CD4+Th17 in the decoction group than in negative control and cyclophosphamide groups (p < 0.05). However, higher serum levels of CD4+CD25+ Treg and Th17/Treg were seen in the decoction group, relative to the negative control and cyclophosphamide groups (p < 0.05). Serum TNF-α was also markedly elevated in decoction group, when compared with negative control and cyclophosphamide groups (p < 0.05). Serum VEGF was markedly lower in decoction group than in negative control and cyclophosphamide groups, and was appreciably lower in cyclophosphamide group than in negative control group (p < 0.05). Conclusion: Yugan Sanjie decoction effectively alleviates clinical symptoms of LC, and improves immune function of mice by regulating serum levels of T lymphocytes. These findings provide scientific support for a new treatment strategy. [ABSTRACT FROM AUTHOR]