Abstract
AIM: Melatonin shows therapeutic benefits in gastric cancer, but the mechanism underlying its anticancer effects remains elusive. The aim of this study was to determine whether melatonin inhibits lung metastasis in gastric cancer.
MAIN METHODS: A lung metastasis model of gastric cancer was established in nude mice injected with human gastric adenocarcinoma MGC80-3 cells. Mice were divided into control, IL-1β-treated, melatonin-treated, and IL-1β plus melatonin-treated groups and analyzed for the formation of lung metastatic nodules by flow cytometry and hematoxylin and eosin staining. The mRNA expression of epithelial-mesenchymal transition (EMT) markers was assessed by RT-qPCR. The activities of matrix metalloproteinase (MMP)-2 and MMP-9 were determined by gelatin zymography and their protein expression by western blotting and immunohistochemistry. The levels of NF-κB p65 and phosphorylated (p)-p65 were detected by immunohistochemistry.
KEY FINDINGS: The number of lung metastases in the IL-1β plus melatonin group was significantly lower and the sizes of nodules were smaller than those in the IL-1β group. Furthermore, melatonin reversed changes in the expression of EMT markers induced by IL-1β by increasing mRNA levels of β-catenin and E-cadherin and decreasing those of fibronectin, vimentin, and Snail compared to IL-1β. Treatment with IL-1β upregulated the expression and activities of MMP-2 and MMP-9 and expression of NF-κB p65 and phospho-p65 (p-p65), but melatonin alleviated these effects.
SIGNIFICANCE: Melatonin inhibited IL-1β-induced lung metastasis of gastric cancer through downregulation of MMP-2, MMP-9, and NF-κB p65 expression and activities. These findings provide a basis for potential use of melatonin as a supplementary therapy for patients with advanced gastric cancer.
See also:
- Official Web Site: The Di Bella Method;
- Melatonin use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;
- About Melatonin - In vitro, review and in vivo publications;
- Publication: Melatonin anticancer effects: Review (from Di Bella's Foundation);
- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);
- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);
- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;
- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);
- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);
- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);
- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;
- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;
- Neuroblastoma: Complete objective response to biological treatment;
- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;
- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;
- Oesophageal squamocellular carcinoma: a complete and objective response;
- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;
- Complete objective response to biological therapy of plurifocal breast carcinoma;