Combining use of phillyrin and autophagy blocker exerts suppressive effect on nasopharyngeal carcinoma cell malignancy and autophagy via AMPK/mTOR/p70s6k signaling pathway

BackgroundNasopharyngeal carcinoma (NPC) is one of the malignant cancers in southern China. Phillyrin is a major active constituent extracted from Forsythia suspensa (Thunb.) and possesses anti-inflammatory and anti-tumor properties.ObjectiveThis study was conducted to clarify the functional role and mechanism of autophagy in the anti-tumor effects induced by phillyrin, as well as the combined effects of phillyrin and the autophagy inhibitor chloroquine (CQ).ResultsPhillyrin dose-dependently suppressed NPC cell viability, whereas promoted cell apoptosis. In addition, phillyrin induced autophagy in NPC cells by increasing Beclin-1 protein expression and LC3-II/I ratio as well as decreasing p62 protein level. Pathway analysis showed that phillyrin enhanced the phosphorylation levels of AMPK but inhibited the phosphorylation of mTOR and p70s6k. Furthermore, the combined use of phillyrin and CQ further suppressed CNE-1 cell viability and promoted cell apoptosis.ConclusionThese findings indicate that inhibition of autophagy by CQ enhances phillyrin-mediated anti-tumor activity in vitro, which may provide a novel strategy to improving the anti-cancer efficacy of drug treatment.