The Expression Of Ifnar1 In Oral Squamous Cell Carcinoma And The Therapeautic Effect Of IFNΑ Mediated By IFNAR1

OBJECTIVES:To investigate the expression of type I interferon receptor 1(IFNAR1)in oral squamous cell carcinoma(OSCC)and normal oral mucosa,and to explore its relationship with clinical pathological characteristics and prognosis.To explore the possible mechanism of IFNAR1 in the treatment of OSCC with IFNα.METHODS:1 The expression of IFNAR1 in 108 cases with OSCC and 16 cases with normal oral mucosa was detected by immunohistochemistry.The relationship between the expression of IFNAR1 in OSCC tissues and clinical pathological characteristics were analyzed.2 The expression of IFNAR1 in HN4 and HN30 cells were inhibited by siRNA,and the interference efficiency was confirmed by Western Bolt and RT-PCR.3 To detect of cell activity.by adding gradient concentration IFNα both in HN4,HN30 and cell down regulation of IFNAR1 through MTT assay.4 Western blot was used to investigate the possible mechanism of IFNα therapy mediated by IFNAR1.RESULTS:1 The expression of IFNAR1 in OSCC was significantly higher than that in normal mucosa.The expression of IFNAR1 was closely correlated with T stage,lymph node metastasis,TNM stage and pathological differentiation(P<0.05).The patients with higher expression of IFNAR1 have poorer prognosis by Log-rank test(P=0.057).2 After transfection with 3 different sequences of siRNA in HN4 and HN30,Western Blot and RT-PCR were used to determine the most efficient interference sequence.3 Cell viability of HN4 and HN30 cells were decreased with the increase of IFNα concentration;the expression of IFNAR1 were decreased by siRNA in HN4 and HN30 cells,and the cell activity of that was higher than control group by adding the same concentration of IFNα.4 Western blot was used to investigate the expression of possible related factors in IFNα therapy,the expression of p-P38 was lower in siIFNAR1 than in si-Scr in both HN4 and HN30 cells.CONCLUSIONS:1 The expression of IFNAR1 in OSCC was significantly higher than that in normal oral mucosa,and it is a potential risk factor for OSCC.It had a tendency to be related to the prognosis of OSCC patients.The IFNAR1 expression in tumor tissues can be a suroggate to select patients who can benefit from interferon alpha treatment in OSCC.2 IFNα had the killing effect on HN4 and HN30 cells,and the killing effect was stronger with the increase of concentration.The down regulation of IFNAR1 expression in HN4 and HN30 cells after transfection with siRNA inhibited the therapeutic effect of IFNα.It shows the therapeutic effect of IFNα on OSCC is mediated by IFNAR1.3 IFNAR1 mediated IFNα therapy may be mediated by p-P38 in HN4 and HN30 cells.