Piperlongumine Downregulates TERT Expression via STAT3 Pathway by Epigenetic Regulation in Gastric Cancer Cells / 胃肠病学

ABSTRACT

Background: Piperlongumine (PL) is an alkaloid compound extracted from piperlongum. Many studies have shown that PL has anti-tumor effects on a variety of tumor cells in vivo and in vitro. However, the specific mechanism needs to be further explored. Aims: To investigate the regulatory mechanism of PL on the expression of TERT in gastric cancer cells. Methods: Gastric cancer cells were treated with different doses of PL, AG490, respectively. CCK-8 and plate colony formation experiment were used to detect cell viability. Real-time fluorescent quantitative PCR was used to detect the expression of TERT mRNA. Western blotting was used to detect the protein expressions of TERT, STAT3, p-STAT3 and DNMT1. TRAP-ELISA was used to determine the telomerase activity. Luciferase reporter gene was used to detect the TERT promoter activity. Results: Compared with control group, gastric cancer cells viability in PL group was significantly decreased, colony formation ability was significantly reduced, TERT mRNA and protein expressions, as well as telomerase activity were significantly reduced, p-STAT3 and DNMT1 protein expressions were significantly downregulated. AG490 significantly inhibited gastric cancer cells viability, protein expressions of p-STAT3, DNMT1 and TERT. Conclusions: PL may inhibit gastric cancer cells viability through regulation of TERT expression via STAT3-mediated epigenetic regulation and it may become a new target drug for the treatment of gastric cancer in future.