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Melatonin Inhibits Gastric Cancer Cell Proliferation by Suppressing Exosome miR-27b-3p Expression

Published on Tuesday, 28 April 2026

Abstract

Background/aim: In addition to its established role in regulating circadian rhythms and reducing inflammation, melatonin has been demonstrated to possess anti-cancer properties. In this study, we investigated the effects of exosomal miRNAs released by melatonin-treated GC cells on gastric cancer.

Materials and methods: To identify the potential exosomal miRNAs involved in the treatment of gastric cancer, we performed exosome small RNA sequencing (sRNA-seq) to screen significant changes in 34 exosomal miRNAs in AGS cells before and after melatonin treatment. CCK-8, wound healing, and transwell invasion assays were used to examine the effects of miRNAs on cancer characteristics. Furthermore, a dual-luciferase reporter gene assay was performed to identify the miRNA targets.

Results: Exosomal miR-27b-3p was down-regulated by approximately 1.37-fold following melatonin treatment. The CCK-8 assay revealed a significant increase in cell proliferation in the miR-27b-3p mimic group compared to that in the miR-27b-3p mimic NC group. In the wound healing assay, cells treated with miR-27b-3p mimics displayed significantly more rapid wound closure than that observed in the miR-27b-3p mimic NC group. The transwell invasion assay revealed a substantial increase in the number of invading cells in the miR-27b-3p mimic group compared to that in the miR-27b-3p mimic NC group. Additional analysis revealed that miR-27b-3p directly targets ADAMTS5 and that its up-regulation results in increased proliferation, invasion, and metastasis of GC cells.

Conclusion: Melatonin suppressed the progression of gastric cancer by regulating the exosomal miR-27b-3p-ADAMTS5 pathway. Thus, melatonin represents a promising potential therapeutic agent for patients with gastric cancer.

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About this publication.

The Di Bella's Method: Use of Melatonin and pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea (together with others chemical compounds) in Oesophageal Cancer:

- Oesophageal squamocellular carcinoma: a complete and objective response;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day and more orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- 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 - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Variable Part - Chondroitin sulfate, up to 3-4 grams per day, orally);

The Di Bella's Method: Use of Melatonin since 1974 with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea and Proteoglycans/Glycosaminoglycans/glucosamine - together with others chemical compounds - in several Oncological Pathologies:

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- A retrospective observational study on cases of Osteosarcomas treated with a multitherapy: The rationale and effectiveness;

- A Retrospective Observational Study on Cases of Sarcoma Treated with the Di Bella Method: Rationale and Effectiveness;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;