联合阻断Stat3和HIF-1α对低氧条件下喉癌细胞放化疗的增敏作用  

Combined inhibition of Stat3 and HIF-1α for enhancement of radio-and chemo-sensitivity in laryngeal squamous cell carcinoma

作　　者：孙亚敬 路秀英[1] 李晓明[1] 

机构地区：[1]白求恩国际和平医院耳鼻咽喉头颈外科,石家庄050082

出　　处：《临床耳鼻咽喉头颈外科杂志》2015年第4期352-356,共5页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

摘　　要：目的:研究信号转导子和转录激活子3(Stat3)和低氧诱导因子-1α(HIF-1α)对低氧条件下喉癌Hep-2细胞放疗及化疗抵抗作用的影响。方法:应用Western blot技术检测低氧条件下喉癌Hep-2细胞中pStat3和HIF-1α蛋白的表达。MTT比色法分别检测单独和联合抑制Stat3和HIF-1α喉癌Hep-2细胞放疗及化疗后细胞的增殖情况。结果:1AG490在体外低氧条件下能够有效抑制Hep-2细胞及稳定转染HIF-1αshRNA的Hep-2(Hep-2HIF-1α-/-)细胞的生长(P<0.05);2抑制Stat3表达后HIF-1α的表达下调(P<0.05);3联合阻断HIF-1α和Stat3信号通路后能增强喉癌Hep-2细胞对放化疗的敏感性。结论:联合阻断HIF-1α和STAT3信号通路较单独阻断HIF-1α或STAT3信号通路能进一步增强喉癌Hep-2细胞对放化疗的敏感性。在有效阻断HIF-1α直接信号通路的同时封闭STAT3旁侧调节通路,有助于进一步提高头颈鳞状细胞癌肿瘤细胞对放化疗的敏感性,并为减少治疗抵抗提供一个新的思路和方法。Objective：To investigate the influence of signal transducer and activator of transcription 3（Stat3）and hypoxia-inducible factor-1α（HIF-1α）on the resistance effect of laryngeal squamous cell carcinoma to radiation therapy and chemotherapy under the hypoxia circumstances.Method：Western blot was used to test the expression of p-Stat3 and HIF-1αin the Hep-2cells under the hypoxia conditions.MTT assay was used to test the proliferation of Hep-2cells after radiation therapy and chemotherapy;the Hep-2cells were suppressed expression of Stat3and/or HIF-1α.Result：1AG490induced significant proliferation inhibition on Hep-2cells and Hep-2HIF-1α-/-cells in vitro underthe hypoxia environments（P〈0.05）;2 Suppressing expression of Stat3 reduced the expression of HIF-1αprotein（P〈0.05）;3Combined inhibition of Stat3 and HIF-1αenhanced radio-and chemo-sensitivity in laryngeal squamous carcinoma cells under hypoxia.Conclusion：Combined inhibition of Stat3 and HIF-1αcan further enhance radio-and chemo-sensitivity in laryngeal squamous carcinoma cells under hypixia compare than inhibiting Stat3 or HIF-1αalone.Effectively blocking of HIF-1αpathway and suppressing the expression of Stat3,would be an effective method to enhance radio-and chemo-sensitivity in laryngeal squamous carcinoma cells,which provides a new thought to reduce the resistance to treatment.

关 键 词：STAT3 低氧诱导因子-1Α 喉肿瘤 顺铂 放疗 

分 类 号：R739.65[医药卫生—肿瘤]