Mechanism of endoplasmic reticulum stress pathway inhibitor salubrinal enhancing the apoptosis of head and neck squamous carcinoma cells / 中华放射肿瘤学杂志

ABSTRACT

Objective To explore the mechanism underlying the effect of endoplasmic reticulum stress pathway inhibitor Salubrinal on enhancing the apoptosis of head and neck squamous carcinoma cells.Methods Three types of head and neck squamous carcinoma cell lines (KB,Fadu,Detroit562) were divided into the control,Salburinal (sal),irradiation (IR) and sal combined with IR (IR+sal) groups.The expression levels of p-ATM/ATM,DNA-PK and cleaved Caspase-3 were quantitatively measured.The cell apoptosis rate was detected among four groups.The effect of Salburinal on cell viability was evaluated by MTT assay.Results Compared with the IR group,the expression level of p-ATM/ATM (t =3.5,8.43 and 9.42,all P＜0.05) was significantly up-regulated,whereas that of DNA-PK (t =9.19,17.44,16.67,all P＜ 0.05) was considerably down-regulated in the IR+sal group.The expression level of cleaved Caspase-3 in the IR+sal group was significantly higher compared with those in the other three groups (t=6.79,9.76 and 9.7g,all P＜0.05).Compared with the IR group,the cell apoptosis rate was significantly enhanced in the IR +sal group (t=5.67,6.95 and 7.28,all P＜0.05).Salubrinal exerted an effect upon the apoptosis of three cell lines in a concentration-and time-dependent manner.Conclusions As an endoplasmic reticulum stress pathway inhibitor,Salubrinal can enhance the apoptosis rate of head and neck squamous carcinoma cells.The underlying mechanism is probably correlated with irradiation-induced DNA double strand injury,suppressing the repairing of DNA damage and thereby increasing the apoptosis of tumor cells.