Network Pharmacology-Based Study on the Mechanism of Bushen-Jianpi Decoction in Liver Cancer Treatment.

To investigate the mechanism of a Bushen-Jianpi decoction (BSJPD) in liver cancer (LC) treatment, we analyzed clinical therapy data, conducted network pharmacology analysis, and performed pharmacological experimental verification in vitro and in vivo. The univariate analysis of clinical therapy showed that the BSJPD was protective factor (p < 0.05). The network pharmacology analysis showed that 9 compounds were important nodes of BSJPD-LC therapy network. In experimental verification, the rate of apoptosis increased in the liver tumors of mice treated with the BSJPD (p < 0.05); drug serum with 20 % BSJPD inhibited cell viability (p < 0.05) and reduced the expression of PI3K, the Bcl-xL/BAD ratio, and the levels of p53 and p-Akt in HepG2 cells. Moreover, licochalcone A, alisol B, and hederagenin inhibited cell viability (p < 0.05), induced cell apoptosis (p < 0.01), reduced p-Akt levels, and increased cleaved-CASP3 (p < 0.05) and p53 expression levels in HepG2 cells. These data suggest that the BSJPD prolongs the survival of LC patients and induces apoptosis and that it may be associated with the regulation of PI3K, Akt, p53, CASP3, and Bcl-xL/BAD expression.

[Regulatory effect of bushen jianpi recipe on cellular immunity of patients with primary liver cancer after intervention therapy].

OBJECTIVE: To observe the regulatory effect of Bushen Jianpi Recipe (BSJPR) on cellular immunity the of primary liver cancer patients of Gan-Shen yin-deficiency and Pi qi-deficiency syndrome type after intervention therapy. METHODS: According to the multi-center randomized controlled principle, 117 patients after transcatheter arterial chemoembolization (TACE) were assigned to two groups, 60 in the treated group and 57 in the control group, who were treated respectively with BSJPR and liver protecting remedy (silymarin and vitamin c) for 12 weeks. Changes in TCM syndrome, quality of life (QOL), immediate effect on tumor size and survival time were observed. Meantime, the cellular immune function was also observed, including the T lymphocyte response determined by 3H-TdR, expression of MHC class I/II and B7 molecule detected by FACS, and interleukin 10 and 12 (IL-10, IL-12), interferon-gamma (IFN-gamma) tested by ELISA. RESULTS: In the treated group after treatment, the efficacy for improving TCM syndrome reached 73.33% (44/60 cases), their half-year survival rate being 83.33% (50/60 cases); while those in the control group were 52.63% (30/57 cases) and 70.18% (40/57 cases) respectively, significant difference was shown between the two groups (P <0.05). The patients' QOL was improved in the treated group after treatment, with no obvious adverse reaction. However, the clinical benefit rate in the control group (92.7%, 51/55 cases) was higher than that in the treated group (78.0%, 46/59 cases, P =0. 035). Laboratory examination showed increases of MHC class II (CD14+/HLA-DR) expression on monocyte surface as well as IFN-gamma and IL-12 production in the treated group. CONCLUSION: Using BSJPR together with TACE could enhance patients' cellular immune function to elevate the clinical curative effect on primary liver cancer.

Myeloid suppressor cell-associated immune dysfunction in CSA1M fibrosarcoma tumor-bearing mice.

CSA1M tumor-bearing mice exhibited a severe immune dysfunction but the underlying mechanism remained unclear. In this study, we demonstrated that the myeloid suppressor cell (Mac-1(+)Gr-1(+) cells)-(MSC) related T cell immunosuppression in this tumor-bearing model. In mice at the late stage of CSA1M tumor-bearing (Late TB [8-10 weeks after cell inoculation in male BALB/c mice]), the percentages for CD4(+) and CD8(+) T cells decreased but Mac-1(+) cells increased in spleens with severe splenomegaly. There was no deficit for concanavalin A-induced CD4(+) and CD8(+) T cell proliferation, interferon-gamma (IFN-gamma) and interleukin (IL)-4 production, but delayed-type hypersensitivity reaction were attenuated. Analysis of cytokine production in unfractionated spleen cells showed a significant reduction of IFN-gamma and a marked increase of IL-10 and IL-4. In Late-TB mice, splenic MSC number intensively accumulated; the mRNA expressions of the signal transducer and activator of transcription 1, interferon regulatory factor 1 (IRF-1), and inducible nitric-oxide synthase (iNOS) were enhanced in MSC; the nitric oxide production and arginase enzyme activity increased in MSC as well. Furthermore, the concanavalin A-induced T cell proliferation was inhibited in the presence of lipopolysaccharide- or IFN-gamma-activated MSC from Late-TB mice, which could be reversed by the iNOS specific inhibitor L-NMMA. iNOS seemed to be required more than arginase for the suppressive activity of MSC. Taken together, our results suggest that the immune dysfunction in tumor-bearing mice might be causally associated with the accumulation of MSC and its tumor-favoring property.