Although cisplatin is one of the chemotherapeutics most frequently used in oral squamous cell carcinoma(OSCC)treatment,it exerts multiple side effects and poor chemosensitivity.Nitrate reportedly demonstrates several ...Although cisplatin is one of the chemotherapeutics most frequently used in oral squamous cell carcinoma(OSCC)treatment,it exerts multiple side effects and poor chemosensitivity.Nitrate reportedly demonstrates several beneficial biological functions,and synthesized nitrates enhance the therapeutic efficacy of chemotherapy.However,the role of inorganic nitrate in cisplatin chemotherapy remains unclear.We therefore investigated the effect of inorganic nitrate exerted on cisplatin sensitivity in OSCC.We found that nitrate did not affect OSCC cell growth and apoptosis in OSCC cells and OSCC xenograft tumor animal studies.Cisplatin induced REDD1 expression and AKT activation in OSCC.However,nitrate could increase cisplatin chemosensitivity,reduce its REDD1 expression,and attenuate AKT signaling activation in OSCC cells.Dysregulation of high levels of REDD1,which could enhance AKT activation,was positively associated with poor prognosis in OSCC patients.Thus,reduced REDD1 expression and retarded AKT activation induced by inorganic nitrate might be a new potential approach to the sensitization of oral cancer to cisplatin treatment in the future.展开更多
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-031)Beijing Hospitals Authority of Hospitals’Mission Plan(SML20151401,Capital Medical University)+1 种基金Beijing Municipality Government grants(Beijing Scholar Program—PXM2020_014226_000005,PXM2019_014226_000039,PXM2019_014226_000011,PXM2018_014226_000021,PXM2017_014226_000023,PXM2018_193312_000006_0028S643_FCG,PXM2016_014226_000034)the National Natural Science Foundation of China(91649124).
文摘Although cisplatin is one of the chemotherapeutics most frequently used in oral squamous cell carcinoma(OSCC)treatment,it exerts multiple side effects and poor chemosensitivity.Nitrate reportedly demonstrates several beneficial biological functions,and synthesized nitrates enhance the therapeutic efficacy of chemotherapy.However,the role of inorganic nitrate in cisplatin chemotherapy remains unclear.We therefore investigated the effect of inorganic nitrate exerted on cisplatin sensitivity in OSCC.We found that nitrate did not affect OSCC cell growth and apoptosis in OSCC cells and OSCC xenograft tumor animal studies.Cisplatin induced REDD1 expression and AKT activation in OSCC.However,nitrate could increase cisplatin chemosensitivity,reduce its REDD1 expression,and attenuate AKT signaling activation in OSCC cells.Dysregulation of high levels of REDD1,which could enhance AKT activation,was positively associated with poor prognosis in OSCC patients.Thus,reduced REDD1 expression and retarded AKT activation induced by inorganic nitrate might be a new potential approach to the sensitization of oral cancer to cisplatin treatment in the future.
