纤维生长因子受体1抑制剂PD173074对鼻咽癌细胞系增殖和凋亡的影响

FGFR1 selective inhibitor PD173074 can reduce proliferation and induce apoptosis of nasopharyngeal carcinoma

目的:研究纤维生长因子受体1(FGFR1)抑制剂PD173074对于鼻咽癌细胞增殖和凋亡的影响。方法:通过免疫印迹和实时定量PCR研究了FGFR1在多种鼻咽癌细胞系中的表达情况;通过MTT法检测了PD173074对CNE细胞增殖抑制的时间-效应关系和浓度-效应关系;通过免疫印迹研究了PD173074对FGFR1及下游AKT的磷酸化水平的影响;通过Caspase3/9活性检测和免疫印迹研究了PD173074对鼻咽癌细胞凋亡的影响及凋亡途径。结果:在CNE、PONE1和C666-1中,CNE细胞系FGFR1表达最高。10nmol/L PD173074刺激36h以上时能够通过抑制FGFR1和其下游的AKT磷酸化水平而抑制CNE细胞的增殖水平。在CNE细胞系中,PD173074刺激36h以上能够活化Caspase9并进一步激活Caspase3,引起细胞凋亡。结论:PD173074通过抑制FGFR1和下游的AKT磷酸化抑制鼻咽癌细胞系CNE的增殖,并激活内源性凋亡途径激活Caspase9,进而激活Caspase3引起CNE细胞凋亡。

Objective：To study the influence of PD173074 on proliferation and apoptosis of nasopharyngeal carcinoma.Method：With immunoblotting and RT-PCR,FGFR1 expression was detected in CNE,PONE1 and C666-1cell lines.With MTT assay,the time-effect and dose-effect correlation between PD173074 and inhibition of CNE proliferation was evaluated.After PD173074 stimulation,the phosphorylation level of FGFR1 and AKT was detected with immunoblotting assay.Furthermore,influence of PD173074 on the activation of Caspase3 and Caspase9was detected to study the underlying mechanism of why PD173074 could inhibit CNE proliferation.Result：FGFR1has the highest expression in CNE cell line.Under incubation of 10nmol/L PD173074 stimulation for 36 hours to 72 hours,the phosphorylation of FGFR1 and AKT was impaired significantly,which further reduced the proliferation of CNE.Moreover,PD173074 can activate the intrinsic apoptotic pathway by stimulating Caspase9,which activated Caspase3 and induced the apoptosis.Conclusion：PD173074could inhibit proliferation of nasopharyngeal carcinoma cell through reducing the phosphorylation of FGFR1 and AKT.Additionally,PD173074 can induce CNE apoptosis by activating intrinsic apoptotic pathway via cleaving Caspase9 and Caspase3.