ABSTRACT
Objective To explore the possibility of rapamycin to up-regulate radiosensitivity of nasopharyngeal carcinoma (NPC) and its molecular mechanism.Methods In vitro,with untreated cells as the control,NPC cells were treated with rapamycin,irradiation (IR),or both rapamycin and IR.Phosphorylation of S6 and GSK3β,expression of Cyclin D1,clonogenic survival,number of residual γH2AX foci,and cell cycle status between study groups were compared.In vivo,athymic mice bearing CNE1 tumor were similarly treated.Tumor weight,Cyclin D1 and phosphorylated S6 in the xenograft model were compared between study groups.Results The results showed that rapamycin alone decreased the phosphorylation of S6 and glycogen synthase kinase 3 β (GSK3β),and the expression of Cyclin D1 in NPC cells.Thus,rapamycin-treated NPC cells had lower cell viability,higher DNA damage and more G1 arrest than the control,which was reflected by the in vivo study that rapamycin significantly attenuated tumor growth and decreased the levels of Cyclin D1 and phosphorylated S6.Moreover,the combination of rapamycin and IR caused the highest cell death,DNA damage,G1 arrest and tumor regression compared to those treated either alone.Conclusions Rapamycin up-regulate NPC radiosensitivity by inhibiting signal transduction of Akt/mammalian target of rapamycin (mTOR)/S6 pathway and Akt/GSK3β pathway,and by downregulating Cyclin D1 expression.
ABSTRACT
Objective To investigate the correlation of platelets-to-lymphocyte ratio (PLR) with neutrophil-to-lymphocyte ratio (NLR) from pretreatment in the Xinjiang Uygur patients with nasopharyngeal carcinoma.Methods In this retrospective analysis,96 cases of nasopharyngeal carcinoma patients with pathologically diagnosis were collected.Receiver operating characteristic (ROC) curve analysis suggested that optimum PLR and NLR cut-off point for nasopharyngeal carcinoma.The patients were divided into high-PLR and low-PLR groups,high-NLR and low-NLR groups,respectively.The survival rate was calculated with Kaplan-Meier method.The Log rank statistics was used to test differences between groups.The prognostic factors that may affect patients with nasopharyngeal carcinoma in Uighur population of Xinjiang were analyzed by COX proportional hazards models.Results For high-PLR and low-PLR groups,5-year overall survival,and progression-free survival were 46.6％ and 79.3％,49.8％ and 82.7％,respectively;the difference was statistically significant (all P ＜ 0.01).For high-NLR and low-NLR groups,5-year overall survival rate,and progression-free survival rate were 41.3％ and 41.3％,50.8％ and 82.5％,respectively;the difference was statistically significant (all P ＜ 0.01).Univariate analysis showed that N stage,clinical stage,NLR,and PLR had significantly impact on overall survival and progression-free survival (all P ＜ 0.05);multivariate analysis showed that PLR and clinical stage had statistical significance in Uighur patients with nasopharyngeal carcinoma for progression-free survival and overall survival (all P ＜ 0.05).Conclusions PLR may be independent factor that influences the prognosis of patients with nasopharyngeal carcinoma in Uighur population of Xinjiang.