ABSTRACT
Background: Hepatocellular carcinoma (HCC) is a malignant tumor harmful to human health. Ganji Fang (GJF) has good clinical efficacy in the treatment of HCC, but its mechanism is still unclear. Objective: The aim of this study was to investigate the mechanism of action of GJF in the treatment of HCC through network pharmacology, molecular docking and in vitro experiments. Methods: A series of network pharmacology methods were used to identify the potential targets and key pathways of GJF in the treatment of HCC. Then, molecular docking technology was used to explore the binding ability of key active ingredients and targets in GJF. Multiple external databases were used to validate the key targets. In in vitro experiments, we performed MTT assays, wound-healing assays, cell cycle assays, apoptosis assays and RTâqPCR to verify the inhibitory effect of GJF on the Human hepatoma G2 (HepG2) cells. Result: A total of 162 bioactive components and 826 protein targets of GJF were screened, and 611 potential targets of HCC were identified. Finally, 63 possible targets of GJF acting on HCC were obtained. KEGG enrichment analyses showed that the top five pathways were the cell cycle, cellular senescence, p53 signaling pathway, PI3K/Akt signaling pathway, and progesterone-mediated oocyte maturation. Among them, we verified the PI3K/Akt signaling pathway. CCNE1, PKN1, CCND2, CDK4, EPHA2, FGFR3, CDK6, CDK2 and HSP90AAI were enriched in the PI3K/Akt pathway. The molecular docking results showed that the docking scores of eight active components of GJF with the two targets were all less than -5.0, indicating that they had certain binding activity. In vitro cell experiments showed that GJF could inhibit the proliferation and migration of HepG2 cells, block the cell cycle and induce apoptosis of HepG2 cells, which may be related to the PI3K/Akt signaling pathway. In summary, EPHA2 may be an important target of GJF in HCC, and pachymic acid may be an important critical active compound of GJF that exerts anticancer activity. Conclusion: In general, we demonstrated, for the first time, that the molecular mechanism of GJF in HCC may involve induction of G0/G1 phase cycle arrest through inhibition of the PI3K/Akt signaling pathway and promote apoptosis of hepatoma cell lines. This study provides a scientific basis for the subsequent clinical application of GJF and the in-depth study of its mechanism.
ABSTRACT
BACKGROUND: Chinese herbal injections (CHIs) have been proven beneficial to patients with non-small cell lung cancer (NSCLC) in combination with chemotherapy. The network meta-analysis (NMA) was designed to update and expand on previous work to better evaluate the effectiveness and safety of different Yiqi Fuzheng (YQFZ) CHIs combined with the Vinorelbine plus cisplatin (NP) regimen versus NP alone for NSCLC. METHODS: We searched multiple electronic databases and identified randomized controlled trials (RCTs) concerning different YQFZ CHIs combined with the NP regimen for treating NSCLC up to March 1st, 2019. The outcomes are the objective response rate, performance status and adverse reactions (ADRs). Two individuals accomplished the quality assessment of this NMA based on the Cochrane risk of bias tool and the methodological section of the CONSORT statement. Random effects models were generated to estimate efficacy and safety outcomes. Odds ratios and corresponding 95% confidence intervals were calculated via Stata 14 software. Furthermore, the rankings for the efficacy and safety of different YQFZ CHIs for each outcome were determined by the surface under the cumulative ranking curve (SUCRA). RESULTS: Initially, a total of 4775 citations were retrieved through comprehensive searching, and 88 eligible articles involving 6695 participants and 8 CHIs were ultimately included. The cluster analysis results of the current evidence indicated that the NP regimen combined with Delisheng, Shenfu and Shenmai injections have a higher clinical effectiveness rate and better performance status compared with the NP regimen alone. Additionally, the NP regimen combined with Shenqifuzheng, Shengmai and Shenfu injections may be considered a favorable choice for reliving ADRs among patients with NSCLC. CONCLUSIONS: The current evidence demonstrated that the combination of Shenfu injection plus NP regimen could produce better outcomes than other YQFZ CHIs groups in terms of efficacy and safety. However, meticulously designed, strictly executed, high-quality trials are still required to further assess and confirm the results due to the inadequacy of the included RCTs.
