Published "Melatonin inhibits proliferation, migration and invasion by inhibiting the PI3K/Akt/mTOR signaling pathway in gallbladder cancer cells to induce ROS-mediated apoptosis", in which it is reported that melatonin is a kind of hormone secreted mainly by the pineal gland. The indole compounds play an important role. Its role in regulating circadian rhythm and cancer treatment.
However, the role of melatonin in gallbladder cancer and its related mechanisms remain unclear. The results show that melatonin inhibits the growth, migration and invasion of gallbladder cancer cells. Subsequently, analysis showed that melatonin significantly induced apoptosis in gallbladder cancer cells and changed the expression of apoptotic proteins, including Bax, Bcl-2, cytochrome C, cleaved caspase-3 and PARP.
Treatment with N-acetyl-L-cysteine or 740 YP significantly reduced the anti-tumor effect of melatonin in NOZ and GBC-SD cells. Finally, melatonin inhibits the growth of GBC-SD cells in an in vivo athymic nude mouse xenograft model.
Dr. Shi Xiaojing and Dr. Zhai Wenlong said: “According to reports, gallbladder cancer is the most aggressive and common pathological type among the widely reported biliary tract cancers.”
Unfortunately, most patients with gallbladder cancer are diagnosed at an advanced stage because the patient has metastases and other symptoms in the advanced stage.
A previous study reported that the 5-year survival rate for GBC was 13%, and the median survival time was less than 1 year. Therefore, there is an urgent need for new drugs and therapeutic targets for inoperable GBC patients.
The synthesis and secretion of melatonin is controlled by light/night clock, which means that light inhibits the synthesis of melatonin, and darkness stimulates its production. After hydroxylation and decarboxylation, tryptophan synthesizes serotonin, which is regulated by tryptophan hydroxylase and decarboxylase. Serotonin is then acetylated, methylated and converted into melatonin in the pineal gland.
Recently, more and more evidences have shown that melatonin can inhibit tumorigenesis, metastasis and drug resistance of a variety of cancers. By reducing the expression of iNOS and COX-2, melatonin limits the damaging effects of inflammation, thereby inhibiting the tumor progression of breast cancer. Melatonin destroys the formation of tumor blood vessels in renal adenocarcinoma by lowering VEGF. However, the relationship between melatonin and gallbladder cancer has not been clearly established.
These authors evaluated the inhibitory effect of melatonin on the proliferation of gallbladder cancer cells.
The Shi/Zhai research team concluded in its American aging research results, “This study shows that melatonin inhibits the proliferation, migration and invasion of gallbladder cancer cells. From a mechanism perspective, in vitro, melatonin promotes ROS mediation. Further studies have shown that melatonin inhibits the phosphorylation of PI3K/Akt/mTOR signaling pathway (Figure 7). In addition, melatonin also inhibits tumor growth in vivo without significant toxicity. Overall, melatonin may be an effective and novel drug candidate for the treatment of gallbladder cancer."
Full text – https://www.aging-us.com/article/203561/text