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

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.

TGFβ1 in Cancer-Associated Fibroblasts Is Associated With Progression and Radiosensitivity in Small-Cell Lung Cancer

“…Pan et al (2006) reported that higher levels of TGFβ1 in tumor cells reduced the tumor growth of glioblastoma cells. These reports were confirmed by Liu et al (2019).…”

An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress

“…Melatonin also hampers vasculogenic mimicry of oral cancer cells via inhibition of ROS-activated Akt and ERKs signaling pathway implicating the HIF-α pathway [48]. Melatonin up-regulates TGF-β1 expression in tumor tissues during the inhibition of gastric cancer tumor growth process [49]. Furthermore, apoptotic and anti-proliferative effects of melatonin on breast cancer cells are mediated by the simultaneous activation of the Apaf-1/caspase-dependent apoptotic pathway and the inhibition of PI3K/Akt, p300/NF-κB, and COX-2/PGE2 signaling pathways [32].…”

Guhong Injection Protects Against Apoptosis in Cerebral Ischemia by Maintaining Cerebral Microvasculature and Mitochondrial Integrity Through the PI3K/AKT Pathway

“…Activation of VEGFR, a member of the receptor tyrosine kinase (RTK) family, will then lead to upregulation of multiple cellular pathways (PI3K/AKT) that promote cell growth and angiogenesis ( Feng et al, 2019 ; Wu et al, 2019 ; Kaufman et al, 2021 ). Transforming growth factor-β1 (TGF-β1) is a polypeptide growth factor that can activate the PI3K/Akt signaling pathway by binding to TβR-I and TβR-II on fibroblasts and other cell membranes and activating receptors ( Li et al, 2012 ; Liu et al, 2019 ). TGF-β1 induces the p85 subunit of PI3K to be recruited into focal adhesion kinase (FAK) ( Vallée and Lecarpentier 2019 ).…”