The Antigastric Cancer Effect of Triptolide is Associated With H19/NF-κB/FLIP Axis

作者：Weiwei Yuan, Jinxi Huang, Shanshan Hou, Huahua Li, Liangyu Bie, Beibei Chen, Gaofeng Li, Yang Zhou, Xiaobing Chen · 发表于：Frontiers in Pharmacology · 年份：2022 · DOI：10.3389/fphar.2022.918588 · 被引用次数：19 · 研究领域：Natural Compounds in Disease Treatment、Cancer-related molecular mechanisms research、Circular RNAs in diseases

Background and Objective: Triptolide (TP), one of the fat-soluble components extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F. (TWHF), possesses strong antitumor bioactivities, but its dose-dependent side effects restrict its wide application. This study was designed to investigate whether inflammatory factors increased the antitumor effects of the nontoxic dose of TP on gastric cancer cells and tried to explore the possible molecular mechanisms. Method: AGS and MKN45 cells were treated with different doses of TP and TNF- α . Cell viability and apoptosis were detected in vitro . In addition, NF-κB mediated prosurvival signals and cytoprotective proteins, especially FLICE-inhibitory protein (FLIP), were detected to determine their effects on TP/TNF- α –induced apoptosis. Moreover, the function of lncRNA H19/miR-204-5p/NF-κB/FLIP axis was investigated in vitro , and the antigastric cancer effect of TP plus TNF- α was proved in the mice xenograft model. Result: In vitro experimental results showed that TP pretreatment promoted apoptosis in AGS and MKN45 cells upon TNF- α exposure. TP/TNF- α –mediated apoptosis was partly mediated by the inhibitory effect of NF-κB–mediated FLIP expression. Oncogene H19 lying in the upstream pathway of NF-κB played a vital role upon TNF- α exposure, and bioinformatics analysis proved that H19 participated in TP/TNF- α –induced apoptosis via binding of miR-204-5p. Lastly, a low dose of TP and TNF- α inhibited the tumor weight...