Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation.

BACKGROUND: Gastric cancer (GC) is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis. Resveratrol, a non-flavonoid polyphenolic compound found in a variety of Chinese medicinal materials, has shown excellent anti-GC effect. However, its exact mechanisms of action in GC have not been clarified. AIM: To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms. METHODS: Action targets of resveratrol and GC-related targets were screened from public databases. The overlapping targets between the two were confirmed using a Venn diagram, and a "Resveratrol-Target-GC" network was constructed using Cytoscape software version 3.9.1. The protein-protein interaction (PPI) network was constructed using STRING database and core targets were identified by PPI network analysis. The Database for Annotation, Visualization and Integrated Discovery database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A "Target-Pathway" network was created by using Cytoscape 3.9.1. The RNA and protein expression levels of core target genes were observed using the Cancer Genome Atlas and the Human Protein Atlas databases. DriverDBv3 and Timer2.0 databases were used for survival and immune infiltration analysis. Subsequently, the findings were further verified by molecular docking technology and in vitro experiments. RESULTS: A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases, and 181 intersection targets between the two were screened by Venn diagram. The top 20 core targets were identified by PPI network analysis of the overlapping targets. GO function analysis mainly involved protein binding, identical protein binding, cytoplasm, nucleus, negative regulation of apoptotic process and response to xenobiotic stimulus. KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, ErbB signaling pathway, etc. FBJ murine osteosarcoma viral oncogene homolog (FOS) and matrix metallopeptidase 9 (MMP9) were selected by differential expression analysis, and they were closely associated with immune infiltration. Molecular docking results showed that resveratrol docked well with these two targets. Resveratrol treatment arrested the cell cycle at the S phase, induced apoptosis, and weakened viability, migration and invasion in a dose-dependent manner. Furthermore, resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression. CONCLUSION: The anti-GC effects of resveratrol are related to the inhibition of cell proliferation, migration, invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

Ultrasonically activated scalpel versus monopolar electrocautery shovel in laparoscopic total mesorectal excision for rectal cancer.

AIM: To investigate the feasibility and safety of monopolar electrocautery shovel (ES) in laparoscopic total mesorectal excision (TME) with anal sphincter preservation for rectal cancer in order to reduce the cost of the laparoscopic operation, and to compare ES with the ultrasonically activated scalpel (US). METHODS: Forty patients with rectal cancer, who underwent laparoscopic TME with anal sphincter preservation from June 2005 to June 2007, were randomly divided into ultrasonic scalpel group and monopolar ES group, prospectively. White blood cells (WBC) were measured before and after operation, operative time, blood loss, pelvic volume of drainage, time of anal exhaust, visual analogue scales (VAS) and surgery-related complications were recorded. RESULTS: All the operations were successful; no one was converted to open procedure. No significant differences were observed in terms of preoperative and postoperative d 1 and d 3 WBC counts (P=0.493, P=0.375, P=0.559), operation time (P=0.235), blood loss (P=0.296), anal exhaust time (P=0.431), pelvic drainage volume and VAS in postoperative d 1 (P=0.431, P=0.426) and d 3 (P=0.844, P=0.617) between ES group and US group. The occurrence of surgery-related complications such as anastomotic leakage and wound infection was the same in the two groups. CONCLUSION: ES is a safe and feasible tool as same as US used in laparoscopic TME with anal sphincter preservation for rectal cancer on the basis of the skillful laparoscopic technique and the complete understanding of laparoscopic pelvic anatomy. Application of ES can not only reduce the operation costs but also benefit the popularization of laparoscopic operation for rectal cancer patients.

Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO3 vehicle alone or CP dissolved in NaHCO3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.