RESUMO
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.
RESUMO
Background: As a kind of squamous cell carcinoma of head and neck (HNSCC), gingival sarcomatoid squamous cell carcinoma (GSSCC) is a rare biphasic malignant neoplasm. To date, surgical resection was often utilized for gingival squamous cell carcinoma (GSCC), while for patients with advanced gingival carcinoma who cannot tolerate surgery, radiotherapy and chemotherapy can be regarded as a treatment strategy. Many molecular-targeted drugs were investigated and approved for the treatment of malignant diseases, including hematologic diseases and solid tumors. Although targeted therapies such as EGFR inhibitors have shown therapeutic efficacy in HNSCC, there are still some patients who cannot benefit from it. New therapeutic targets and strategies should be further explored. Case presentation: An 83-year-old woman was referred to our hospital with left lower gingival mass for more than 1 month in June 2021. Pathologic diagnosis is sarcomatoid squamous cell carcinoma. Due to the large tumor at the time of diagnosis and poor quality of life, the patient was intolerant to surgery, so she was given radiotherapy (RT) combined with concurrent chemotherapy (CT) with albumin bound paclitaxel. According to next-generation sequencing (NGS) results (MET exon 14 skipping mutation-positive), she was treated with crizotinib, a tyrosine kinase inhibitor that targets MET. Through the comprehensive treatment, the patient's condition promptly improved, clinical complete remission (CR) was achieved in 2 months, and 9-month progression-free survival (PFS) was obtained. She finally died from non-cancer-related diseases. Conclusion: Here we report the treatment of a GSSCC patient with MET mutation, who responded to crizotinib promptly and positively. It provides a new reference for understanding MET abnormalities in GSSCC and offers a new idea for the targeted treatment of gingival carcinoma.