[Mechanism of Modified Huoluo Xiaoling Pills against colorectal cancer based on network pharmacology, molecular docking, and experimental validation].

This study aims to predict the possible targets and related signaling pathways of Modified Huoluo Xiaoling Pills against colorectal cancer(CRC) by both network pharmacology and molecular docking and verify the mechanism of action by experiments. TCMSP was used to obtain the active ingredients and targets of Modified Huoluo Xiaoling Pills, and GeneCards, DrugBank, OMIM, and TTD were employed to acquire CRC-related targets. Cytoscape software was utilized to construct the drug-active ingredient-target network, and the STRING database was applied to establish the protein-protein interaction(PPI) network. DAVID platform was adopted to investigate the targets in terms of GO function and KEGG pathway enrichment analysis. Molecular docking was performed in AutoDock Vina. HCT 116 cells were intervened by different concentrations of Modified Huoluo Xiaoling Pills-containing serum, and CCK-8 was used to detect the proliferation inhibition of HCT 116 cells in each group. Transwell was employed to show the invasive abi-lity of HCT 116 cells, and Western blot was taken to reveal the expression levels of ß-catenin, cyclinD1, c-Myc, as well as epithelial-mesenchymal transition(EMT) marker proteins E-cadherin, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST in HCT 116 cells. The network pharmacological analysis yielded 242 active ingredients of Modified Huoluo Xiaoling Pills, 1 844 CRC targets, and 127 overlapping targets of CRC and Modified Huoluo Xiaoling Pills, and the signaling pathways related to CRC involved PI3K-Akt, TNF, HIF-1, IL-17, Wnt, etc. Molecular docking showed that the key active ingredients had a stable binding conformation with the core proteins. CCK-8 indicated that Modified Huoluo Xiaoling Pills significantly inhibited the proliferation of HCT 116 cells. Transwell assay showed that with increasing concentration of Modified Huoluo Xiaoling Pills containing serum, the invasive ability of HCT 116 cells was more obviously inhibited. The expression of ß-catenin, cyclinD1, c-Myc, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST proteins were suppressed, and the expression of E-cadherin was improved by the intervention of drug-containing serum. Thus, it can be seen that Modified Huoluo Xiaoling Pills restrains the proliferation, invasion, and metastasis of CRC cells through multiple components, multiple targets, and multiple pathways, and the mechanism of action may be related to the inhibition of the activation of the Wnt/ß-catenin signaling pathway, thereby affecting the occurrence of EMT.

[Meta-analysis of acupuncture and moxibustion for the therapeutic effect on postoperative gastrointestinal dysfunction of gastric cancer].

OBJECTIVE: To systematically review the therapeutic effect of acupuncture and moxibustion on postoperative gastrointestinal dysfunction (GID) of gastric cancer with meta-analysis. METHODS: The articles of randomized controlled trials (RCTs) of acupuncture and moxibustion treatment for postoperative GID of gastric cancer were retrieved from the following databases from the time of database establishment to December 31, 2020, including PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database and China Biomedical Literature Database (SinoMed). RevMan5.3 software was used for meta-analysis. Using Stata16.0 software, sensitivity analysis and publication bias test were performed. RESULTS: A total of 16 RCTs were included finally, including 1 360 patients, of which, there were 681 cases in the intervention group and 679 cases in the control group. Meta-analysis results showed that acupuncture and moxibustion shortened the time of first flatus (P<0.000 01, MD =-14.52, 95%CI = [-17.31, -11.74]), the time of first bowel sound (P<0.000 01, MD =-10.50, 95%CI =[-13.99, -7.01]) and the time of first defecation (P<0.000 1, MD =-13.79, 95%CI =[-20.09, -7.50]). Meanwhile, acupuncture and moxibustion shortened the time of the first food intake (P<0.000 1, MD =-3.23, 95%CI = [-3.45, -3.00]) and the hospital stay (P<0.000 01, MD =-1.94, 95%CI =[-2.20, -1.69]) after gastric cancer operation, and reduced the incidences of postoperative adverse reactions, i.e. nausea and vomiting (P =0.000 3, RR =0.43, 95%CI =[0.28, 0.68]) and abdominal distention (P =0.000 5, RR =0.41, 95%CI =[0.25, 0.68]). CONCLUSION: Acupuncture and moxibustion can promote the recovery of postoperative gastrointestinal function in the patients with gastric cancer. But, for the comparison among different measures of acupuncture and moxibustion intervention, it needs more high-quality trials for a further verification.