Role of transforming growth factor β1 in the inhibition of gastric cancer cell proliferation by melatonin in vitro and in vivo

Published on Wednesday, 26 August 2020

Abstract

Transforming growth factor β (TGF‑β) is a polypeptide growth factor with various biological activities, and is widely distributed in various tissues. In mammals, TGF‑β has three isoforms: TGF‑β1, 2, and 3, of which TGF‑β1 is most abundant in the TGF‑β family. TGF‑β1 is closely related to the occurrence and development of tumors.

A large number of previous studies have shown that melatonin can inhibit a variety of malignancies. Thus, the aim of the present study was to investigate the role of TGF‑β1 in the melatonin‑mediated inhibition of the proliferation of gastric cancer cells in vitro and in vivo.

TGF‑β1 cytokine stimulation, anti‑TGF‑β1 neutralizing antibody blocking, siRNA TGF‑β1 and other means were utilized to explore the role of TGF‑β1 during the course of anti‑gastric cancer by melatonin.

The results showed that melatonin upregulated the expression of TGF‑β1 in tumor tissues during the process of inhibiting gastric cancer tumor growth in vivo.

Melatonin inhibited the proliferation of gastric cancer cells in vitro, accompanied by increased expression of TGF‑β1 in a time‑dependent manner. siRNA‑mediated silencing of TGF‑β1 and anti‑TGF‑β1 neutralizing antibody completely blocked the TGF‑β1 pathway, which significantly antagonized the melatonin‑mediated inhibition of the growth and proliferation of gastric cancer cells, and promoted G1 phase to S phase transformation of MFC cells.

Our findings suggest that TGF‑β1 is involved in the regulation of the proliferation of tumor cells.

One of the ways in which melatonin inhibits the proliferation of gastric cancer cells is dependent on the TGF‑β1 signaling pathway.

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- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day 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 - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- 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 Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- 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, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (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);