Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.

Origanum vulgare L.leaf extract alleviates finasteride-induced oxidative stress in mouse liver and kidney

Objective:To investigate the hepatorenoprotective effects of Origanum vulgare L.against finasteride-induced oxidative injury in the liver and kidney of mice.Methods:Liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI/MS)analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents.Thirty BALB/c mice received 0.5 mL/day distilled water,finasteride(25 mg/kg/day for 10 d),and 100,200,or 400 mg/kg/day finasteride+Origanum vulgare extract with 6 mice per group for five weeks.On day 36,liver and kidney function as well as pro-and antiinflammatory(IFN-γ,IL-12,IL-6,TNF-α,IL-1β,and IL-10)cytokines were measured.The total antioxidant status,nitric oxide(NO),and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated.Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities.Results:Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS.Origanum vulgare extract,especially at 200 and 400 mg/kg/day doses,significantly improved liver and kidney biochemical indices,decreased inflammatory cytokines,increased total antioxidant status and NO synthase and catalase activities,as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group.Histopathological results further confirmed the protective effect of Origanum vulgare extract.Conclusions:Origanum vulgare extract ameliorates finasterideinduced hepatic and renal biochemical and histopathological alterations,and restores antioxidant/oxidant balance.