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.

Plasma metabolic profiling on postoperative colorectal cancer patients with different traditional Chinese medicine syndromes.

OBJECTIVES: This study aims to investigate the metabolic profiles of postoperative colorectal cancer (PCRC) patients with different traditional Chinese medicine (TCM) syndromes and to discuss the metabolic mechanism under PCRC progression and TCM syndrome classification. METHODS: Fifty healthy controls (HC) and 70 PCRC patients, including 10 Dampness and heat syndrome (DHS), 33 Spleen deficiency syndrome (SDS), 19 Liver and kidney Yin deficiency syndrome (LKYDS) and 8 with non-TCM syndrome (NS) were enrolled. Plasma metabolic profiles were detected by Gas chromatography-mass spectrometry (GC-MS) and analyzed by principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Furthermore, pathway enrichment was analyzed based on KEGG and DAVID databases and metabolic network was constructed via metaboanalyst and cytoscape. RESULTS: The top-3 metabolites with higher abundance in PCRC compared with HC were terephthalic acid (165.417-fold), ornithine (24.484-fold) and aminomalonic acid (21.346-fold). And the cholesterol (0.588-fold) level was decreased in PCRC. l-Alanine, 1, 2-ethanediamine, urea, glycerol, glycine, aminomalonic acid, creatinine and palmitic acid were specifically altered in the DHS, while d-tryptophan was exclusively changed in SDS, and l-proline, 1, 2, 3-propanetricarboxylic acid, d-galactose and 2-indolecarboxylic acids in LKYDS. CONCLUSIONS: The plasma metabolic profiles were perturbed in PCRC patients. Increased levels of terephthalic acid might indicate high risk of relapse and elevated ornithine may contribute to the post-operational recovery or may raise the susceptibility to PCRC recurrence. The metabolic profiles of DHS, SDS, LKYDS and NS were almost separately clustered, indicating the possibility of explaining TCM syndromes classification using metabolomics. Furthermore, creatinine and aminomalonic acid alternation might correlate with the formation of DHS, while d-tryptophan may associate with SDS and d-galactose and 1, 2, 3-propanetricarboxylic acid may relate to LKYDS. As numbers of patients in each TCM syndrome are small, further study is needed to verify those results.

Research advances in traditional Chinese medicine syndromes in cancer patients.

Traditional Chinese medicine (TCM) syndrome, also known as TCM ZHENG or TCM pattern, is an integral and essential part of TCM theory that helps to guide the design of individualized treatments. A TCM syndrome, in essence, is a characteristic profile of all clinical manifestations in one patient that can be readily identified by a TCM practitioner. In this article, the authors reviewed the presentations of TCM syndromes in seven common malignancies (liver, lung, gastric, breast, colorectal, pancreatic and esophageal cancers), the objectivity and the standardization of TCM syndrome differentiation, the evaluation of TCM syndrome modeling in cancer research, and syndrome differentiation-guided TCM treatment of cancers. A better understanding of TCM syndrome theory, as well as its potential biological basis, may contribute greatly to the clinical TCM diagnosis and the treatment of cancer.

Zuo Jin Wan reverses P-gp-mediated drug-resistance by inhibiting activation of the PI3K/Akt/NF-κB pathway.

BACKGROUND: Zuo-Jin-Wan (ZJW), a traditional Chinese medicine formula, has been identified to be effective against drug resistance in cancer. In the present study, we investigated the effect of ZJW on acquired oxaliplatin-resistant and the PI3K/Akt/NF-κB pathway in vitro. METHODS: We tested the dose-response relationship of ZJW on reversing drug-resistance by CCK-8 assay and flow cytometry analysis in vitro. The protein expression of P-gp, MRP-2, LRP, and ABCB1 mRNA expression level were evaluated by Western blot and quantitative RT-PCR. The activities of PI3K/Akt/NF-κB pathway were also examined with or without ZJW, including Akt, IκB, p65 and their phosphorylation expression. RESULTS: We found that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs and increased oxaliplatin (L-OHP)-induced cell apoptosis in a time- and dose-dependent manner. Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. The effect of ZJW in reversing drug-resistance and suppressing phosphorylation of Akt (Ser473) and NF-κB were weakened after treatment with a PI3K/Akt activator in HCT116/L-OHP cells. CONCLUSIONS: Our study has provided the first direct evidence that ZJW reverses drug-resistance in human colorectal cancer by blocking the PI3K/Akt/NF-κB signaling pathway, and could be considered as a useful drug for cancer therapy.

[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.