Role of transforming growth factor beta 1 in the inhibition of gastric cancer cell proliferation by melatonin in vitro and in vivo

摘要

Transforming growth factor beta (TGF-beta) is a polypeptide growth factor with various biological activities, and is widely distributed in various tissues. In mammals, TGF-beta has three isoforms: TGF-beta 1, 2, and 3, of which TGF-beta 1 is most abundant in the TGF-beta family. TGF-beta 1 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-beta 1 in the melatonin-mediated inhibition of the proliferation of gastric cancer cells in vitro and in vivo. TGF-beta 1 cytokine stimulation, anti-TGF-beta 1 neutralizing antibody blocking, siRNA TGF-beta 1 and other means were utilized to explore the role of TGF-beta 1 during the course of anti-gastric cancer by melatonin. The results showed that melatonin upregulated the expression of TGF-beta 1 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-beta 1 in a time-dependent manner. siRNA-mediated silencing of TGF-beta 1 and anti-TGF-beta 1 neutralizing antibody completely blocked the TGF-beta 1 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-beta 1 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-beta 1 signaling pathway.